Tecentriq

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 
 
 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tecentriq 840 mg concentrate for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One 14 mL vial of concentrate contains 840 mg of atezolizumab*. 
 
After dilution (see section 6.6), the final concentration of the diluted solution should be between 3.2 
and 16.8 mg/mL. 
 
*Atezolizumab is an Fc-engineered, humanised IgG1 anti-programmed death-ligand 1 (PD-L1) 
monoclonal antibody produced in Chinese hamster ovary cells by recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
 
Clear, colourless to slightly yellowish liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or 
metastatic urothelial carcinoma (UC): 
• after prior platinum-containing chemotherapy, or 
• who are considered cisplatin ineligible, and whose tumours have a PD-L1 expression ≥ 5% (see 

section 5.1). 
 
Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or 
metastatic NSCLC after prior chemotherapy. Patients with EGFR mutant or ALK-positive NSCLC 
should also have received targeted therapies before receiving Tecentriq (see section 5.1). 
 
Tecentriq in combination with nab-paclitaxel is indicated for the treatment of adult patients with 
unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumours have 
PD-L1 expression ≥ 1% and who have not received prior chemotherapy for metastatic disease. 
 
4.2 Posology and method of administration 
 
Tecentriq must be initiated and supervised by physicians experienced in the treatment of cancer. 
 
PD-L1 testing for patients with UC or TNBC 
 
Patients with previously untreated UC and TNBC should be selected for treatment based on the 
tumour expression of PD-L1 confirmed by a validated test (see section 5.1). 



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Posology 
 
Tecentriq monotherapy 
 
The recommended dose of Tecentriq is: 
• 840 mg administered intravenously every two weeks, or 
• 1,680 mg administered intravenously every four weeks.  
 
Tecentriq in combination with nab-paclitaxel in 1L mTNBC 
 
The recommended dose of Tecentriq is 840 mg administered by intravenous infusion, followed by 
100 mg/m2 nab-paclitaxel. For each 28-day cycle, Tecentriq is administered on days 1 and 15, and 
nab-paclitaxel is administered on days 1, 8, and 15. Refer to the full prescribing information for the 
combination product (see also section 5.1). 
 
Duration of treatment 
 
It is recommended that patients are treated with Tecentriq until loss of clinical benefit (see section 5.1) 
or unmanageable toxicity. 
For TNBC, it is recommended that patients are treated with Tecentriq until disease progression or 
unmanageable toxicity (see section 5.1). 
 
Delayed or missed doses 
 
If a planned dose of Tecentriq is missed, it should be administered as soon as possible. The schedule 
of administration must be adjusted to maintain the appropriate interval between doses.  
  
Dose modifications during treatment 
 
Dose reductions of Tecentriq are not recommended. 
 
Dose delay or discontinuation (see also sections 4.4 and 4.8) 
 
Table 1: Dose modification advice for Tecentriq 
 

Immune related adverse 
reaction 

Severity Treatment modification 

Pneumonitis 
 

Grade 2 Withhold Tecentriq 
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks, and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

 Grade 3 or 4 Permanently discontinue Tecentriq 



4 
 
 

Immune related adverse 
reaction 

Severity Treatment modification 

Hepatitis in patients without 
hepatocellular carcinoma 
(HCC)  
 
 
 

Grade 2: 
(ALT or AST > 3 to 5 x upper limit of 
normal [ULN] 
 
or 
 
blood bilirubin > 1.5 to 3 x ULN) 
 

Withhold Tecentriq 
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 3 or 4: 
(ALT or AST > 5 x ULN 
 
or 
 
blood bilirubin > 3 x ULN) 

Permanently discontinue Tecentriq 

Hepatitis in patients with 
HCC 

If AST/ALT is within normal limits at 
baseline and increases to >3x to ≤10x 
ULN  
 
or 
 
If AST/ALT is >1 to ≤3x ULN at 
baseline and increases to >5x to ≤10x 
ULN 
 
or 
 
If AST/ALT is >3x to ≤5x ULN at 
baseline and increases to  >8x to ≤10x 
ULN 

Withhold Tecentriq  
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

If AST/ALT increases to >10x ULN  
 
or  
 
total bilirubin increases to >3x ULN 

Permanently discontinue Tecentriq 

Colitis 
 

Grade 2 or 3 Diarrhoea (increase of ≥ 4 
stools/day over baseline) 
 
or 
 
Symptomatic Colitis 

Withhold Tecentriq  
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 4 Diarrhoea or Colitis (life 
threatening; urgent intervention 
indicated) 

Permanently discontinue Tecentriq 

Hypothyroidism or 
hyperthyroidism 
 

Symptomatic Withhold Tecentriq 
 
Hypothyroidism: 
Treatment may be resumed when 
symptoms are controlled by thyroid 
replacement therapy and TSH levels 
are decreasing 
 
Hyperthyroidism: 
Treatment may be resumed when 
symptoms are controlled by anti-
thyroid medicinal product and 
thyroid function is improving 



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Immune related adverse 
reaction 

Severity Treatment modification 

Adrenal insufficiency 
 

Symptomatic 
 

Withhold Tecentriq 
 
Treatment may be resumed when the 
symptoms improve to Grade 0 or 
Grade 1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day and patient is stable on 
replacement therapy 

Hypophysitis Grade 2 or 3 Withhold Tecentriq 
 
Treatment may be resumed when the 
symptoms improve to Grade 0 or 
Grade 1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day and patient is stable on 
replacement therapy 

Grade 4 Permanently discontinue Tecentriq 
Type 1 diabetes mellitus Grade 3 or 4 hyperglycaemia (fasting 

glucose > 250 mg/dL or 
13.9 mmol/L) 
 
 

Withhold Tecentriq 
 
Treatment may be resumed when 
metabolic control is achieved on 
insulin replacement therapy 

Infusion-related reactions 
 

Grade 1 or 2 Reduce infusion rate or interrupt. 
Treatment may be resumed when the 
event is resolved 

Grade 3 or 4 Permanently discontinue Tecentriq 
Rash 
 

Grade 3 Withhold Tecentriq  
 
Treatment may be resumed when 
rash is resolved and corticosteroids 
have been reduced to ≤ 10 mg 
prednisone or equivalent per day 

Grade 4 Permanently discontinue Tecentriq 
Myasthenic 
syndrome/myasthenia 
gravis, Guillain-Barré 
syndrome and 
Meningoencephalitis 
 

All Grades Permanently discontinue Tecentriq 

Pancreatitis Grade 3 or 4 serum amylase or lipase 
levels increased (> 2 x ULN) 
or Grade 2 or 3 pancreatitis 
 

Withhold Tecentriq  
 
Treatment may be resumed when 
serum amylase and lipase levels 
improve to Grade 0 or Grade 1 
within 12 weeks, or symptoms of 
pancreatitis have resolved, and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 4 or any grade of recurrent 
pancreatitis 

Permanently discontinue Tecentriq 



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Immune related adverse 
reaction 

Severity Treatment modification 

Myocarditis Grade 2 Withhold Tecentriq  
 
Treatment may be resumed when the 
symptoms improve to Grade 0 or 
Grade 1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 3 or 4 Permanently discontinue Tecentriq 
Nephritis Grade 2: 

(creatinine level > 1.5 to 3.0 x baseline 
or > 1.5 to 3.0 x ULN) 

Withhold Tecentriq 
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 3 or 4: 
(creatinine level > 3.0 x baseline or > 
3.0 x ULN) 

Permanently discontinue Tecentriq 
 

Myositis Grade 2 or 3 Withhold Tecentriq 
Grade 4 or grade 3 recurrent myositis Permanently discontinue Tecentriq 

Other immune-related 
adverse reactions 

Grade 2 or Grade 3 Withhold until adverse reactions 
recovers to Grade 0-1 within 12 
weeks, and corticosteroids have been 
reduced to ≤ 10 mg prednisone or 
equivalent per day. 

Grade 4 or recurrent Grade 3 Permanently discontinue Tecentriq 
(except endocrinopathies controlled 
with replacement hormones) 

Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for 
Adverse Event Version 4.0 (NCI-CTCAE v.4.).  
 
Special populations 
 
Paediatric population  
 
The safety and efficacy of Tecentriq in children and adolescents aged below 18 years have not been 
established. Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation 
on a posology can be made. 
 
Elderly 
 
Based on a population pharmacokinetic analysis, no dose adjustment of Tecentriq is required in 
patients ≥ 65 years of age (see sections 4.8 and 5.1).  
 
Renal impairment 
 
Based on a population pharmacokinetic analysis, no dose adjustment is required in patients with mild 
or moderate renal impairment (see section 5.2). Data from patients with severe renal impairment are 
too limited to draw conclusions on this population. 
 
Hepatic impairment 
 
Based on a population pharmacokinetic analysis, no dose adjustment is required for patients with mild 
or moderate hepatic impairment. Tecentriq has not been studied in patients with severe hepatic 
impairment (see section 5.2). 



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Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 
 
Patients with ECOG performance status ≥ 2 were excluded from the clinical trials in NSCLC, TNBC 
2nd line UC and HCC (see sections 4.4 and 5.1, for HCC see sections 4.4 and 5.1 of the Tecentriq 
1,200 mg concentrate for solution for infusion SmPC). 
 
Method of administration  
 
Tecentriq is for intravenous use. The infusions must not be administered as an intravenous push or 
bolus. 
 
The initial dose of Tecentriq must be administered over 60 minutes. If the first infusion is well 
tolerated, all subsequent infusions may be administered over 30 minutes. 
 
For instructions on dilution and handling of the medicinal product before administration, see 
section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to atezolizumab or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the trade name and the batch 
number of the administered product should be clearly recorded in the patient file. 
 
Immune-related adverse reactions 
 
Most immune-related adverse reactions occurring during treatment with atezolizumab were reversible 
with interruptions of atezolizumab and initiation of corticosteroids and/or supportive care. 
Immune-related adverse reactions affecting more than one body system have been observed. 
Immune-related adverse reactions with atezolizumab may occur after the last dose of atezolizumab. 
 
For suspected immune-related adverse reactions, thorough evaluation to confirm aetiology or exclude 
other causes should be performed. Based on the severity of the adverse reaction, atezolizumab should 
be withheld and corticosteroids administered. Upon improvement to Grade ≤ 1, corticosteroid should 
be tapered over ≥ 1 month. Based on limited data from clinical studies in patients whose 
immune-related adverse reactions could not be controlled with systemic corticosteroid use, 
administration of other systemic immunosuppressants may be considered. 
 
Atezolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction 
that recurs and for any Grade 4 immune-related adverse reactions, except for endocrinopathies that are 
controlled with replacement hormones (see sections 4.2 and 4.8). 
 
Immune-related pneumonitis  
 
Cases of pneumonitis, including fatal cases, have been observed in clinical trials with atezolizumab 
(see section 4.8). Patients should be monitored for signs and symptoms of pneumonitis and causes 
other than immune-related pneumonitis should be ruled out. 
. 



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Treatment with atezolizumab should be withheld for Grade 2 pneumonitis, and 1 to 2 mg/kg/day 
prednisone or equivalent should be started. If symptoms improve to ≤ Grade 1, corticosteroids should 
be tapered over ≥ 1 month. Treatment with atezolizumab may be resumed if the event improves to 
≤ Grade 1 within 12 weeks, and corticosteroids have been reduced to ≤ 10 mg prednisone or 
equivalent per day. Treatment with atezolizumab must be permanently discontinued for Grade 3 or 4 
pneumonitis. 
 
Immune-related hepatitis  
 
Cases of hepatitis, some leading to fatal outcomes have been observed in clinical trials with 
atezolizumab (see section 4.8). Patients should be monitored for signs and symptoms of hepatitis. 
 
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin should be monitored 
prior to initiation of treatment, periodically during treatment with atezolizumab and as indicated based 
on clinical evaluation. 
 
For patients without HCC, treatment with atezolizumab should be withheld if Grade 2 event (ALT or 
AST > 3 to 5 x ULN or blood bilirubin > 1.5 to 3 x ULN) persists for more than 5 to 7 days, and 1 to 
2 mg/kg/day of prednisone or equivalent should be started. If the event improves to ≤ Grade 1, 
corticosteroids should be tapered over ≥ 1 month.  
 
Treatment with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued for Grade 3 or Grade 4 events (ALT or AST 
> 5.0 x ULN or blood bilirubin > 3 x ULN). 
 
For patients with HCC, treatment with atezolizumab should be withheld if ALT or AST increases to 
> 3 to ≤10 x ULN from normal limits at baseline, or > 5 to ≤10 x ULN from > 1 ULN to ≤3 x ULN at 
baseline, or > 8 to ≤10 x ULN from > 3 ULN to ≤5 x ULN at baseline, and persists for more than 5 to 
7 days, and 1 to 2 mg/kg/day of prednisone or equivalent should be started. If the event improves to 
≤ Grade 1, corticosteroids should be tapered over ≥ 1 month.  
 
Treatment with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued if ALT or AST increases to  > 10 x ULN or total 
bilirubin increases > 3 x ULN). 
 
Immune-related colitis 
 
Cases of diarrhoea or colitis have been observed in clinical trials with atezolizumab (see section 4.8). 
Patients should be monitored for signs and symptoms of colitis.  
 
Treatment with atezolizumab should be withheld for Grade 2 or 3 diarrhoea (increase of ≥ 4 stools/day 
over baseline) or colitis (symptomatic). For Grade 2 diarrhoea or colitis, if symptoms persist > 5 days 
or recur, treatment with 1 to 2 mg/kg/day prednisone or equivalent should be started. For 
Grade 3 diarrhoea or colitis, treatment with intravenous corticosteroids (1 to 2 mg/kg/day 
methylprednisolone or equivalent) should be started. Once symptoms improve, treatment with 
1 to 2 mg/kg/day of prednisone or equivalent should be started. If symptoms improve to ≤ Grade 1, 
corticosteroids should be tapered over ≥ 1 month. Treatment with atezolizumab may be resumed if the 
event improves to ≤ Grade 1 within 12 weeks and corticosteroids have been reduced to ≤ 10 mg 
prednisone or equivalent per day. Treatment with atezolizumab must be permanently discontinued for 
Grade 4 (life threatening; urgent intervention indicated) diarrhoea or colitis. 
 



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Immune-related endocrinopathies  
 
Hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis and type 1 diabetes mellitus, 
including diabetic ketoacidosis have been observed in clinical trials with atezolizumab (see section 
4.8).  
 
Patients should be monitored for clinical signs and symptoms of endocrinopathies. Thyroid function 
should be monitored prior to and periodically during treatment with atezolizumab. Appropriate 
management of patients with abnormal thyroid function tests at baseline should be considered. 
 
Asymptomatic patients with abnormal thyroid function tests can receive atezolizumab. For 
symptomatic hypothyroidism, atezolizumab should be withheld and thyroid hormone replacement 
should be initiated as needed. Isolated hypothyroidism may be managed with replacement therapy and 
without corticosteroids. For symptomatic hyperthyroidism, atezolizumab should be withheld and an 
anti-thyroid medicinal product should be initiated as needed. Treatment with atezolizumab may be 
resumed when symptoms are controlled and thyroid function is improving. 
 
For symptomatic adrenal insufficiency, atezolizumab should be withheld and treatment with 
intravenous corticosteroids (1 to 2 mg/kg/day methylprednisolone or equivalent) should be started. 
Once symptoms improve, treatment with 1 to 2 mg/kg/day of prednisone or equivalent should follow. 
If symptoms improve to ≤ Grade 1, corticosteroids should be tapered over ≥ 1 month. Treatment may 
be resumed if the event improves to ≤ Grade 1 within 12 weeks and corticosteroids have been reduced 
to ≤ 10 mg prednisone or equivalent per day and the patient is stable on replacement therapy (if 
required). 
 
For Grade 2 or Grade 3 hypophysitis, atezolizumab should be withheld and treatment with intravenous 
corticosteroids (1 to 2 mg/kg/day methylprednisolone or equivalent) should be started, and hormone 
replacement should be initiated as needed. Once symptoms improve, treatment with 1 to 2 mg/kg/day 
of prednisone or equivalent should follow. If symptoms improve to ≤ Grade 1, corticosteroids should 
be tapered over ≥ 1 month. Treatment may be resumed if the event improves to ≤ Grade 1 within 
12 weeks and corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day and the 
patient is stable on replacement therapy (if required). Treatment with atezolizumab should be 
permanently discontinued for Grade 4 hypophysitis. 
 
Treatment with insulin should be initiated for type 1 diabetes mellitus. For ≥ Grade 3 hyperglycaemia 
(fasting glucose > 250 mg/dL or 13.9 mmol/L), atezolizumab should be withheld. Treatment with 
atezolizumab may be resumed if metabolic control is achieved on insulin replacement therapy. 
 
Immune-related meningoencephalitis  
 
Meningoencephalitis has been observed in clinical trials with atezolizumab (see section 4.8). Patients 
should be monitored for clinical signs and symptoms of meningitis or encephalitis. 
 
Treatment with atezolizumab must be permanently discontinued for any grade of meningitis or 
encephalitis. Treatment with intravenous corticosteroids (1 to 2 mg/kg/day methylprednisolone or 
equivalent) should be started. Once symptoms improve, treatment with 1 to 2 mg/kg/day of prednisone 
or equivalent should follow.  
 
Immune-related neuropathies 
 
Myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome, which may be life threatening, 
were observed in patients receiving atezolizumab. Patients should be monitored for symptoms of 
motor and sensory neuropathy.  
 



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Treatment with atezolizumab must be permanently discontinued for any grade of myasthenic 
syndrome / myasthenia gravis or Guillain-Barré syndrome. Initiation of systemic corticosteroids (at a 
dose of 1 to 2 mg/kg/day of prednisone or equivalent) should be considered. 
 
Immune-related pancreatitis 
 
Pancreatitis, including increases in serum amylase and lipase levels, has been observed in clinical 
trials with atezolizumab (see section 4.8). Patients should be closely monitored for signs and 
symptoms that are suggestive of acute pancreatitis. 
 
Treatment with atezolizumab should be withheld for ≥ Grade 3 serum amylase or lipase levels 
increased (> 2 x ULN), or Grade 2 or 3 pancreatitis, and treatment with intravenous corticosteroids  
(1 to 2 mg/kg/day methylprednisolone or equivalent) should be started. Once symptoms improve, 
treatment with 1 to 2 mg/kg/day of prednisone or equivalent should follow. Treatment with 
atezolizumab may be resumed when serum amylase and lipase levels improve to ≤ Grade 1 within 
12 weeks, or symptoms of pancreatitis have resolved, and corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent per day. Treatment with atezolizumab should be permanently 
discontinued for Grade 4, or any grade of recurrent pancreatitis. 
 
Immune-related myocarditis 
 
Myocarditis has been observed in clinical trials with atezolizumab (see section 4.8). Patients should be 
monitored for signs and symptoms of myocarditis.  
 
Treatment with atezolizumab should be withheld for Grade 2 myocarditis, and treatment with systemic 
corticosteroids at a dose of 1 to 2mg/kg/day of prednisone or equivalent should be started. Treatment 
with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks, and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued for Grade 3 or 4 myocarditis. 
 
Immune-related nephritis 
 
Nephritis has been observed in clinical trials with atezolizumab (see section 4.8). Patients should be 
monitored for changes in renal function.  
 
Treatment with atezolizumab should be withheld for Grade 2 nephritis, and treatment with systemic 
corticosteroids at a dose of 1 to 2mg/kg/day of prednisone or equivalent should be started. Treatment 
with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks, and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued for Grade 3 or 4 nephritis. 
 
Immune-related myositis  
 
Cases of myositis, including fatal cases, have been observed in clinical trials with atezolizumab (see 
section 4.8). Patients should be monitored for signs and symptoms of myositis.  
 
Treatment with atezolizumab should be withheld for Grade 2 or 3 myositis and corticosteroid therapy 
(1-2 mg/kg/day prednisone or equivalent) should be initiated. If symptoms improve to ≤ Grade 1, taper 
corticosteroids as clinically indicated. Treatment with atezolizumab may be resumed if the event 
improves to ≤ Grade 1 within 12 weeks, and corticosteroids have been reduced to ≤ 10 mg oral 
prednisone or equivalent per day. Treatment with atezolizumab should be permanently discontinued 
for Grade 4 or grade 3 recurrent myositis, or when unable to reduce the corticosteroid dose to the 
equivalent of ≤ 10 mg prednisone per day within 12 weeks after onset. 
 



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Infusion-related reactions 
 
Infusion-related reactions have been observed with atezolizumab (see section 4.8).  
 
The rate of infusion should be reduced or treatment should be interrupted in patients with Grade 1 or 2 
infusion-related reactions. Atezolizumab should be permanently discontinued in patients with Grade 3 
or 4 infusion-related reactions. Patients with Grade 1 or 2 infusion-related reactions may continue to 
receive atezolizumab with close monitoring; premedication with antipyretic and antihistamines may be 
considered.  
 
Disease-specific precautions 
 
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin in metastatic non 
squamous non small cell lung cancer  
 
Physicians should carefully consider the combined risks of the four-drug regimen of atezolizumab 
bevacizumab, paclitaxel, and carboplatin before initiating treatment (see section 4.8). 
 
Use of atezolizumab in combination with nab-paclitaxel in metastatic triple negative breast cancer 
 
Neutropenia and peripheral neuropathies occurring during treatment with atezolizumab and nab-
paclitaxel may be reversible with interruptions of nab-paclitaxel. Physicians should consult the nab-
paclitaxel summary of product characteristics (SmPC) for specific precautions and contraindications 
of this medicine. 
 
Use of atezolizumab in urothelial carcinoma for previously untreated patients who are considered 
cisplatin ineligible 
 
The baseline and prognostic disease characteristics of the IMvigor210 Cohort 1 study population were 
overall comparable to patients in the clinic who would be considered cisplatin ineligible but would be 
eligible for a carboplatin-based combination chemotherapy. There are insufficient data for the 
subgroup of patients that would be unfit for any chemotherapy; therefore atezolizumab should be used 
with caution in these patients, after careful consideration of the potential balance of risks and benefits 
on an individual basis. 
 
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin  
 
Patients with NSCLC that had clear tumour infiltration into the thoracic great vessels or clear 
cavitation of pulmonary lesions, as seen on imaging, were excluded from the pivotal clinical study 
IMpower150 after several cases of fatal pulmonary haemorrhage were observed, which is a known 
risk factor of treatment with bevacizumab.  
 
In the absence of data, atezolizumab should be used with caution in these populations after careful 
evaluation of the balance of benefits and risks for the patient. 
 
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin in EGFR+ patients 
with NSCLC who have progressed on erlotinib+bevacizumab 
 
In study IMpower150, there are no data on the efficacy of atezolizumab in combination with 
bevacizumab, paclitaxel and carboplatin in EGFR+ patients who have progressed previously on 
erlotinib+bevacizumab.  
 



12 
 
 

Use of atezolizumab in combination with bevacizumab in hepatocellular carcinoma 
 
Data in HCC patients with Child-Pugh B liver disease treated with atezolizumab in combination with 
bevacizumab are very limited and there are currently no data available in HCC patients with Child-
Pugh C liver disease.  
 
Patients treated with bevacizumab have an increased risk of haemorrhage, and cases of severe 
gastrointestinal haemorrhage, including fatal events, were reported in patients with hepatocellular 
carcinoma (HCC) treated with atezolizumab in combination with bevacizumab. In patients with HCC, 
screening for and subsequent treatment of oesophageal varices should be performed as per clinical 
practice prior to starting treatment with the combination of atezolizumab and bevacizumab. 
Bevacizumab should be permanently discontinued in patients who experience Grade 3 or 4 bleeding 
with the combination treatment. Please refer to the bevacizumab Summary of Product Characteristics. 
 
Diabetes mellitus can occur during treatment with atezolizumab in combination with bevacizumab. 
Physicians should monitor blood glucose levels prior to and periodically during treatment with 
atezolizumab in combination with bevacizumab as clinically indicated. 
 
Patients excluded from clinical trials 
 
Patients with the following conditions were excluded from clinical trials: a history of autoimmune 
disease, history of pneumonitis, active brain metastasis, HIV, hepatitis B or hepatitis C infection, 
significant cardiovascular disease and patients with inadequate hematologic and end-organ function.  
Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment; systemic 
immunostimulatory agents within 4 weeks or systemic immunosuppressive medicinal products within 
2 weeks prior to study entry; therapeutic oral or IV antibiotics within 2 weeks prior to initiation of 
study treatment were excluded from clinical trials.  
 
Patient card 
 
All prescribers of Tecentriq must be familiar with the Physician Information and Management 
Guidelines. The prescriber must discuss the risks of Tecentriq therapy with the patient. The patient 
will be provided with the patient card and instructed to carry the card at all times. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No formal pharmacokinetic drug interaction studies have been conducted with atezolizumab. Since 
atezolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions 
are expected.  
 
The use of systemic corticosteroids or immunosuppressants before starting atezolizumab should be 
avoided because of their potential interference with the pharmacodynamic activity and efficacy of 
atezolizumab. However, systemic corticosteroids or other immunosuppressants can be used to treat 
immune-related adverse reactions after starting atezolizumab (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential have to use effective contraception during and for 5 months after 
treatment with atezolizumab. 
 
Pregnancy 
 
There are no data from the use of atezolizumab in pregnant women. No developmental and 
reproductive studies were conducted with atezolizumab. Animal studies have demonstrated that 



13 
 
 

inhibition of the PD-L1/PD-1 pathway in murine pregnancy models can lead to immune-related 
rejection of the developing foetus resulting in foetal death (see section 5.3). These results indicate a 
potential risk, based on its mechanism of action, that administration of atezolizumab during pregnancy 
could cause foetal harm, including increased rates of abortion or stillbirth.  
 
Human immunoglobulins G1 (IgG1) are known to cross the placental barrier and atezolizumab is an 
IgG1; therefore, atezolizumab has the potential to be transmitted from the mother to the developing 
foetus.  
 
Atezolizumab should not be used during pregnancy unless the clinical condition of the woman 
requires treatment with atezolizumab. 
 
Breast-feeding 
 
It is unknown whether atezolizumab is excreted in human milk. Atezolizumab is a monoclonal 
antibody and is expected to be present in the first milk and at low levels afterwards. A risk to the 
newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding 
or to discontinue Tecentriq therapy taking into account the benefit of breast-feeding for the child and 
the benefit of therapy for the woman. 
 
Fertility 
 
No clinical data are available on the possible effects of atezolizumab on fertility. No reproductive and 
development toxicity studies have been conducted with atezolizumab; however, based on the 26-week 
repeat dose toxicity study, atezolizumab had an effect on menstrual cycles at an estimated AUC 
approximately 6 times the AUC in patients receiving the recommended dose and was reversible (see 
section 5.3). There were no effects on the male reproductive organs. 
 
4.7 Effects on ability to drive and use machines 
 
Tecentriq has minor influence on the ability to drive and use machines. Patients experiencing fatigue 
should be advised not to drive and use machines until symptoms abate (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of atezolizumab as monotherapy is based on pooled data in 3,568 patients across multiple 
tumour types. The most common adverse reactions (> 10%) were fatigue (34.5%), decreased appetite 
(24.0%), nausea (22.4%), pyrexia (20.1%), diarrhoea (19.9%), cough (19.8%), rash (19.8%), dyspnoea 
(19.0%), musculoskeletal pain (14.7%), back pain (14.4%), vomiting (14.1%), pruritis (14.0%), 
asthenia (13.9%), arthralgia (13.6%), urinary tract infection (13.1%) and headache (10.9%). 
 
The safety of atezolizumab given in combination with other medicinal products, has been evaluated in 
4,371 patients across multiple tumour types. The most common adverse reactions (≥ 20%) were 
anaemia (36.8 %), neutropenia (35.8 %), nausea (34.4 %), fatigue (33.0 %), thrombocytopenia 
(27.7 %), rash (27.2%), diarrhoea (27.1 %), alopecia (26.4%), constipation (25.7 %), decreased 
appetite (25.0%), and peripheral neuropathy (23.0 %). 
 
For the description of Tecentriq trials, refer to the Tecentriq 1,200 mg concentrate for solution for 
infusion Summary of Product Characteristics (SmPC) section 5.1. 
 
Further details on serious adverse reactions are provided in Section 4.4 Warnings & Precautions. 
 



14 
 
 

Tabulated list of adverse reactions  
 
The Adverse Drug Reactions (ADRs) are listed by MedDRA system organ class (SOC) and categories 
of frequency in Table 2 for atezolizumab given as monotherapy or as combination therapy. Adverse 
reactions known to occur with atezolizumab or chemotherapies given alone may occur during 
treatment with these medicinal products in combination, even if these reactions were not reported in 
clinical trials with combination therapy. The following categories of frequency have been used: very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000), very rare (< 1/10,000). Within each frequency grouping, adverse reactions are presented in 
the order of decreasing seriousness. 
 
Table 2: Summary of adverse reactions occurring in patients treated with atezolizumab 
 

Atezolizumab monotherapy Atezolizumab in combination therapy 
Infections and infestations 
Very common urinary tract infectiona lung infectionb 

Common  sepsisaj 

Blood and lymphatic system disorders 
Very common  anaemia, thrombocytopeniad, neutropeniae, 

leukopeniaf 
Common thrombocytopeniad lymphopeniag 

Immune system disorders 
Common infusion-related reactionh  infusion-related reactionh 

Endocrine disorders 
Very common  hypothyroidismi 
Common hypothyroidismi hyperthyroidismj 

Uncommon hyperthyroidismj, diabetes 
mellitusk, adrenal insufficiencyl 

 

Rare hypophysitism  

Metabolism and nutrition disorders  
Very common decreased appetite decreased appetite  

Common hypokalaemiaae, hyponatraemiaaf, 
hyperglycaemia 

hypokalaemiaae, hyponatraemiaaf, 
hypomagnesaemian 

Nervous system disorders  
Very Common headache peripheral neuropathyo , headache 
Common  syncope, dizziness 
Uncommon Guillain-Barré syndromep, 

meningoencephalitisq 
 

Rare myasthenic syndromer  

Eye Disorders 

Rare uveitis  

Cardiac disorders 

Rare myocarditiss  



15 
 
 

Atezolizumab monotherapy Atezolizumab in combination therapy 
Vascular disorders 
Very common  hypertensionai 

Common hypotension  

Respiratory, thoracic, and mediastinal disorders 
Very common cough, dyspnoea dyspnoea, cough 

Common pneumonitist, hypoxiaag, nasal 
congestion, nasopharyngitis 

dysphonia 

Gastrointestinal disorders 
Very common nausea, vomiting, diarrhoeau nausea, diarrhoeau, constipation, vomiting  

Common abdominal pain, colitisv, 
dysphagia, oropharyngeal painw 

stomatitis, dysgeusia 

Uncommon pancreatitisx  

Hepatobiliary disorders 
Common AST increased, ALT increased, 

hepatitisy 
AST increased, ALT increased 

Skin and subcutaneous tissue disorders 
Very Common rashz, pruritus rashz, pruritus, alopeciaah 

Common dry skin  

Uncommon psoriasis psoriasis 

Musculoskeletal and connective tissue disorders 
Very common arthralgia, back pain, 

musculoskeletal painaa 
arthralgia, musculoskeletal painaa, back pain 

Uncommon Myositisab  

Renal and urinary disorders 
Common blood creatinine increasedc proteinuriaac, blood creatinine increasedc 

Rare nephritisad  

General disorders and administration site conditions 

Very Common pyrexia, fatigue, asthenia pyrexia, fatigue, asthenia, oedema peripheral 

Common influenza like illness, chills  

Investigations 

Common  blood alkaline phosphatase increased 
a Includes reports of urinary tract infection, cystitis, pyelonephritis, escherichia urinary tract infection, urinary 
tract infection bacterial, kidney infection, pyelonephritis acute, urinary tract infection fungal, urinary tract 
infection pseudomonal. 
b Includes reports of pneumonia, bronchitis, lung infection, lower respiratory tract infection, infective 
exacerbation of COPD, infectious pleural effusion, tracheobronchitis, atypical pneumonia, lung abscess, 
paracancerous pneumonia, pyopneumothorax, pleural infection.  
c Includes reports of blood creatinine increased, hypercreatininaemia. 



16 
 
 

d Includes reports of thrombocytopenia, platelet count decreased. 
e Includes reports of neutropenia, neutrophil count decreased, febrile neutropenia, neutropenic sepsis, 
granulocytopenia. 
f Includes reports of white blood cell count decreased, leukopenia. 
g Includes reports of lymphopenia, lymphocyte count decreased 
h Includes reports of  infusion related reaction, cytokine release syndrome, hypersensitivity, anaphylaxis. 
i Includes reports of autoimmune hypothyroidism, autoimmune thyroiditis, blood thyroid stimulating hormone 
abnormal, blood thyroid stimulating hormone decreased, blood thyroid stimulating hormone increased, euthyroid 
sick syndrome, goitre, hypothyroidism, myxoedema coma, thyroid disorder, thyroid function test abnormal, 
thyroiditis, thyroxine decreased, thyroxine free decreased, thyroxine free increased, thyroxine increased, tri-
iodothyronine decreased, tri-iodothyronine free abnormal, tri-iodothyronine free decreased, tri-iodothyronine 
free increased, silent thyroiditis, thyroiditis chronic.  
j Includes reports of hyperthyroidism, Basedow’s disease, endocrine ophthalmopathy, exophthalmos. 
k Includes reports of diabetes mellitus, type 1 diabetes mellitus, diabetic ketoacidosis, ketoacidosis. 
l Includes reports of adrenal insufficiency, primary adrenal insufficiency. 
m Incudes reports of hypophysitis, temperature regulation disorder. 
n Includes reports of hypomagnesaemia, blood magnesium decreased. 
o Includes reports of neuropathy peripheral, autoimmune neuropathy, peripheral sensory neuropathy, 
polyneuropathy, herpes zoster, peripheral motor neuropathy, neuralgic amyotrophy, peripheral sensorimotor 
neuropathy, toxic neuropathy, axonal neuropathy, lumbosacral plexopathy, neuropathic arthropathy, peripheral 
nerve infection. 
p Includes reports of Guillain-Barré syndrome, demyelinating polyneuropathy. 
q Includes reports of encephalitis, meningitis, photophobia. 
r Incudes reports of myasthenia gravis. 
s Reported in studies outside the pooled dataset. The frequency is based on the program wide exposure. 
t Includes reports of pneumonitis, lung infiltration, bronchiolitis, interstitial lung disease, radiation pneumonitis. 
u Includes reports of diarrhoea, defaecation urgency, frequent bowel movements, diarrhoea haemorrhagic. 
v Includes reports of colitis, autoimmune colitis, colitis ischaemic, colitis microscopic, colitis ulcerative. 
w Includes reports of oropharyngeal pain, oropharyngeal discomfort, throat irritation. 
x Includes reports of autoimmune pancreatitis, pancreatitis, pancreatitis acute, lipase increased, amylase 
increased. 
y Includes reports of ascites, autoimmune hepatitis, hepatocellular injury, hepatitis, hepatitis acute, 
hepatotoxicity, liver disorder, drug-induced liver injury, hepatic failure, hepatic steatosis, hepatic lesion, 
oesophageal varices haemorrhage, varices oesophageal. 
z Includes reports of acne, acne pustular, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis bullous, 
dermatitis exfoliative generalised, drug eruption, eczema, eczema infected, erythema, erythema multiforme, 
erythema of eyelid, exfoliative rash, folliculitis, furuncle,  palmar-plantar erythrodysaesthesia syndrome, rash , 
rash erythematous, rash follicular, rash generalised, rash macular, rash maculo-papular, rash papular, rash 
pruritic, rash pustular, rash vesicular, seborrhoeic dermatitis, skin exfoliation, skin toxicity, skin ulcer, toxic 
epidermal necrolysis, toxic skin eruption. 
aa Includes reports of musculoskeletal pain, myalgia, bone pain. 
ab Includes reports of myositis, rhabdomyolysis, polymyalgia rheumatica, dermatomyositis, muscle abscess, 
myoglobin urine present. 
ac Includes reports of proteinuria, protein urine present, haemoglobinurea, urine abnormality, nephrotic 
syndrome, albuminuria. 
ad Includes report of nephritis, Henoch-Schonlein Purpura nephritis. 
ae Includes report of hypokalaemia, blood potassium decreased. 
af Includes report of hyponatraemia, blood sodium decreased. 
ag Includes report of hypoxia, oxygen saturation decreased. 
ah Includes report of alopecia, madarosis, alopecia areata, alopecia totalis, hypotrichosis. 
ai Includes reports of hypertension, blood pressure increased, hypertensive crisis, blood pressure systolic 
increased, diastolic hypertension, blood pressure inadequately controlled, retinopathy hypertensive, hypertensive 
nephropathy, essential hypertension. 
aj Includes  reports of sepsis, septic shock, urosepsis, neutropenic sepsis, pulmonary sepsis, bacterial sepsis, 
klebsiella sepsis, abdominal sepsis, candida sepsis, escherichia sepsis, pseudomonal sepsis, staphylococcal 
sepsis. 
 



17 
 
 

Description of selected adverse reactions 
 
The data below reflect information for significant adverse reactions for atezolizumab as monotherapy 
in clinical studies (see section 5.1). Details for the significant adverse reactions for atezolizumab when 
given in combination are presented if clinically relevant differences were noted in comparison to 
atezolizumab monotherapy. The management guidelines for these adverse reactions are described in 
sections 4.2 and 4.4. 
 
Immune-related pneumonitis 
 
Pneumonitis occurred in 2.8% (99/3,568) of patients who received atezolizumab monotherapy. Of the 
99 patients, one experienced a fatal event. The median time to onset was 4.0 months (range 3 days to 
24.8 months). The median duration was 1.6 months (range 0 day to 21.7+ months; + denotes a 
censored value). Pneumonitis led to discontinuation of atezolizumab in 15 (0.4%) patients. 
Pneumonitis requiring the use of corticosteroids occurred in 1.5% (53/3,568) of patients receiving 
atezolizumab monotherapy.  
 
Immune-related hepatitis  
 
Hepatitis occurred in 1.8% (66/3,568) of patients who received atezolizumab monotherapy. Of the 66 
patients, two experienced a fatal event. The median time to onset was 1.5 months (range 6 days to 18.8 
months). The median duration was 2.1 months (range 0 day to 22.0+ months; + denotes a censored 
value). Hepatitis led to discontinuation of atezolizumab in 9 (0.3%) patients. Hepatitis requiring the 
use of corticosteroids occurred in 0.5% (19/3,568) of patients receiving atezolizumab monotherapy.  
 
Immune-related colitis 
 
Colitis occurred in 1.2% (43/3,568) of patients who received atezolizumab monotherapy. The median 
time to onset was 5.0 months (range 15 days to 17.2 months). The median duration was 1.2 months 
(range 3 days to 17.8+ months; + denotes a censored value). Colitis led to discontinuation of 
atezolizumab in 15 (0.4%) patients. Colitis requiring the use of corticosteroids occurred in 0.5% 
(19/3,568) of patients receiving atezolizumab monotherapy.  
 
Immune-related endocrinopathies  
 
Thyroid disorders  
 
Hypothyroidism occurred in 6.0% (214/3,568) of patients who received atezolizumab monotherapy. 
The median time to onset was 4.4 months (range: 0 day to 31.3 months). Hyperthyroidism occurred in 
1.3% (47/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 
2.1 months (range 21 days to 15.7 months).  
 
Adrenal insufficiency 
 
Adrenal insufficiency occurred in 0.4% (13/3,568) of patients who received atezolizumab 
monotherapy. The median time to onset was 5.7 months (range: 3 days to 19 months). The median 
duration was 16.8 months (range: 0 day to 20.9+ months; + denotes a censored value). Adrenal 
insufficiency led to discontinuation of atezolizumab in 1 (<0.1%) patient. Adrenal insufficiency 
requiring the use of corticosteroids occurred in 0.3% (10/3,568) of patients receiving atezolizumab 
monotherapy. 
 
Hypophysitis 
 
Hypophysitis occurred in < 0.1% (3/3,568) of patients who received atezolizumab monotherapy. The 
median time to onset 5.3 months (range: 24 days to 13.7 months). Two (<0.1%) patients required the 
use of corticosteroids and treatment with atezolizumab was discontinued in 1 (<0.1%) patient. 



18 
 
 

 
Hypophysitis occurred in 0.8% (3/393) of patients who received atezolizumab with bevacizumab, 
paclitaxel, and carboplatin. The median time to onset was 7.7 months (range: 5.0 to 8.8 months). Two 
patients required the use of corticosteroids. 
 
Hypophysitis occurred in 0.4% (2/473) of patients who received atezolizumab in combination with 
nab-paclitaxel and carboplatin. The median time to onset was 5.2 months (range: 5.1 to 5.3 months). 
Both patients required the use of corticosteroids.  
 
Diabetes mellitus  
 
Diabetes mellitus occurred in 0.3% (11/3,568) of patients who received atezolizumab monotherapy. 
The median time to onset was 4.2 months (range 3 days to 9.9 months). Diabetes mellitus led to the 
discontinuation of atezolizumab in < 0.1% (3/3,568) patients. 
 
Diabetes mellitus occurred in 2.0% (10/493) of HCC patients who received atezolizumab in 
combination with bevacizumab. The median time to onset was 4.4 months (range: 1.2 months - 8.3 
months). No events of diabetes mellitus led to atezolizumab withdrawal. 
 
Immune-related meningoencephalitis  
 
Meningoencephalitis occurred in 0.4% (14/3,568) of patients who received atezolizumab 
monotherapy. The median time to onset was 15 days (range: 0 day to 12.5 months). The median 
duration was 21 days (range 6 days to 14.5+ months; + denotes a censored value).  
 
Meningoencephalitis requiring the use of corticosteroids occurred in 0.2% (6/3,568) of patients 
receiving atezolizumab and four patients discontinued atezolizumab.  
 
Immune-related neuropathies 
 
Guillain-Barré syndrome and demyelinating polyneuropathy occurred in 0.1% (5/3,568) of patients 
who received atezolizumab monotherapy. The median time to onset was 7 months (range: 18 days to 
8.1 months). The median duration was 8.0 months (range 18 days to 8.3+ months; + denotes a 
censored value). Guillain-Barré syndrome led to discontinuation of atezolizumab in 1 patient (< 0.1%). 
Guillain-Barré syndrome requiring the use of corticosteroids occurred in < 0.1% (2/3,568) of patients 
receiving atezolizumab monotherapy. 
 
Myasthenic syndrome  
 
Myasthenia gravis occurred in < 0.1% (1/3,568) of patients who received atezolizumab monotherapy. 
The time to onset was 1.2 months.  
 
Immune-related pancreatitis 
 
Pancreatitis, including amylase increased and lipase increased, occurred in 0.8% (27/3,568) of patients 
who received atezolizumab monotherapy. The median time to onset was 4.3 months (range: 0 days to 
16.9 months). The median duration was 27 days (range 3 days to 22.4+ months; + denotes a censored 
value). Pancreatitis led to the discontinuation of atezolizumab in 3 (< 0.1%) patients. Pancreatitis 
requiring the use of corticosteroids occurred in 0.1% (4/3,568) of patients receiving atezolizumab 
monotherapy. 
 



19 
 
 

Immune-related myocarditis  
 
Myocarditis occurred in < 0.1% (2/8,000) of patients across all atezolizumab clinical trials in multiple 
tumour types and treatment combinations. The time to onset was 18 and 33 days. Both patients 
required corticosteroids and discontinued atezolizumab.  
 
Immune-related nephritis 
 
Nephritis occurred in 0.2% (8/3,568) of patients who received atezolizumab. The median time to onset 
was 6.0 months (range: 2.0 to 17.5 months). Nephritis led to discontinuation of atezolizumab in 
4/3,568 (0.1%) patients. Two (<0.1%) patients required corticosteroids. 
 
Immune-related myositis 
 
Myositis occurred in 0.4% (15/3,568) of patients who received atezolizumab monotherapy. The 
median time to onset was 2.9 months (range: 0.4 to 11.0 months). The median duration was 3.8 
months (range 3 days to 22.6+ months; + denotes a censored value). Myositis led to discontinuation of 
atezolizumab in 1 (<0.1%) patient. Seven (0.2%) patients required the use of corticosteroids.  
 
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin  
 
In the first-line NSCLC study (IMpower150), an overall higher frequency of adverse events was 
observed in the four-drug regimen of atezolizumab, bevacizumab, paclitaxel, and carboplatin 
compared to atezolizumab, paclitaxel and carboplatin, including Grade 3 and 4 events (63.6% 
compared to 57.5%), Grade 5 events (6.1% compared to 2.5%), adverse events of special interest to 
atezolizumab (52.4% compared to 48.0%), as well as adverse events leading to withdrawal of any 
study treatment (33.8% compared to 13.3%). Nausea, diarrhoea, stomatitis, fatigue, pyrexia, mucosal 
inflammation, decreased appetite, weight decreased, hypertension and proteinuria were reported 
higher (≥5% difference) in patients receiving atezolizumab in combination with bevacizumab, 
paclitaxel and carboplatin. Other clinically significant adverse events which were observed more 
frequently in the atezolizumab, bevacizumab, paclitaxel, and carboplatin arm were epistaxis, 
haemoptysis, cerebrovascular accident, including fatal events. 
 
Immunogenicity 
 
Across multiple phase III studies, 13.1% to 36.4% of patients developed treatment-emergent anti-drug 
antibodies (ADAs).  
 
Across pooled datasets for patients treated with atezolizumab monotherapy (N=2705) and with 
combination therapies (N= 2285), the following rates of adverse events (AEs) have been observed for 
the ADA-positive population compared to the ADA-negative population, respectively: Grade 3-4 AEs 
49.1% vs. 44.3%,  Serious Adverse Events (SAEs) 42.4% vs. 37.6%, AEs leading to treatment 
withdrawal 6.1% vs 6.7% (for monotherapy); Grade 3-4 AEs 63.9% vs. 60.9%, SAEs 43.9% vs. 
35.6%, AEs leading to treatment withdrawal 22.8% vs 18.4% (for combination therapy). However, 
available data do not allow firm conclusions to be drawn on possible patterns of adverse drug 
reactions.  
 
Paediatric population 
 
The safety of atezolizumab in children and adolescents has not been established. No new safety signals 
were observed in a clinical study with 69 paediatric patients (<18 years) and the safety profile was 
comparable to adults. 
 



20 
 
 

Elderly patients 
 
No overall differences in safety were observed between patients ≥ 65 years of age and younger 
patients receiving atezolizumab monotherapy. In study IMpower150, age ≥ 65 was associated with an 
increased risk of developing adverse events in patients receiving atezolizumab in combination with 
bevacizumab, carboplatin and paclitaxel. 
 
In studies IMpower150 and IMpower133, data for patients ≥75 years of age are too limited to draw 
conclusions on this population. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
There is no information on overdose with atezolizumab.  
 
In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, 
and appropriate symptomatic treatment instituted. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies. ATC code: L01XC32 
 
Mechanism of action 
 
Programmed death-ligand 1 (PD-L1) may be expressed on tumour cells and/or tumour-infiltrating 
immune cells, and can contribute to the inhibition of the antitumour immune response in the tumour 
microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T-cells and antigen 
presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production.  
 
Atezolizumab is an Fc-engineered, humanised immunoglobulin G1 (IgG1) monoclonal antibody that 
directly binds to PD-L1 and provides a dual blockade of the PD-1 and B7.1 receptors, releasing 
PD-L1/PD-1 mediated inhibition of the immune response, including reactivating the antitumour 
immune response without inducing antibody-dependent cellular cytotoxicity. Atezolizumab spares the 
PD-L2/PD-1 interaction allowing PD-L2/PD-1 mediated inhibitory signals to persist.  
 
Clinical efficacy and safety 
 
For the description of studies with Tecentriq administered every 3 weeks at 1,200 mg, refer to the 
Tecentriq 1,200 mg concentrate for solution for infusion SmPC. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


21 
 
 

Duration of treatment 
 
Treatment with atezolizumab until loss of clinical benefit was permitted as defined by the following 
criteria: 
• Absence of symptoms and signs (including worsening of laboratory values [e.g., new or 

worsening hypercalcaemia]) indicating unequivocal progression of disease 
• No decline in ECOG performance status  
• Absence of tumour progression at critical anatomical sites (e.g., leptomeningeal disease) that 

cannot be readily managed and stabilised by protocol-allowed medical interventions prior to 
repeat dosing 

• Evidence of clinical benefit as assessed by the investigator 
 
Patients with locally advanced or metastatic UC who are ineligible for cisplatin therapy and locally 
advanced unresectable or metastatic TNBC were treated with atezolizumab until disease progression. 
 
Urothelial carcinoma 
 
IMvigor211 (GO29294): Randomised trial in locally advanced or metastatic UC patients previously 
treated with chemotherapy 
 
A phase III, open-label, multi-center, international, randomised study, (IMvigor211), was conducted to 
evaluate the efficacy and safety of atezolizumab compared with chemotherapy (investigator’s choice 
of vinflunine, docetaxel, or paclitaxel) in patients with locally advanced or metastatic UC who 
progressed during or following a platinum-containing regimen. This study excluded patients who had 
a history of autoimmune disease; active or corticosteroid-dependent brain metastases; administration 
of a live, attenuated vaccine within 28 days prior to enrolment; and administration of systemic 
immunostimulatory agents within 4 weeks or systemic immunosuppressive medicinal product within 
2 weeks prior to enrolment. Tumour assessments were conducted every 9 weeks for the first 54 weeks, 
and every 12 weeks thereafter. Tumour specimens were evaluated prospectively for PD-L1 expression 
on tumour-infiltrating immune cells (IC) and the results were used to define the PD-L1 expression 
subgroups for the analyses described below.  
 
A total of 931 patients were enrolled. Patients were randomised (1:1) to receive either atezolizumab or 
chemotherapy. Randomisation was stratified by chemotherapy (vinflunine vs. taxane), PD-L1 
expression status on IC (< 5% vs. ≥ 5%), number of prognostic risk factors (0 vs. 1-3), and liver 
metastases (yes vs. no). Prognostic risk factors included time from prior chemotherapy of < 3 months, 
ECOG performance status > 0 and haemoglobin < 10 g/dL. 
 
Atezolizumab was administered as a fixed dose of 1,200 mg by intravenous infusion every 3 weeks. 
No dose reduction of atezolizumab was allowed. Patients were treated until loss of clinical benefit as 
assessed by the investigator or unacceptable toxicity. Vinflunine was administered 320 mg/m2 by 
intravenous infusion on day 1 of each 3-week cycle until disease progression or unacceptable toxicity. 
Paclitaxel was administered 175 mg/m2 by intravenous infusion over 3 hours on day 1 of each 3-week 
cycle until disease progression or unacceptable toxicity. Docetaxel was administered 75 mg/m2 by 
intravenous infusion on day 1 of each 3-week cycle until disease progression or unacceptable toxicity. 
For all treated patients, the median duration of treatment was 2.8 months for the atezolizumab arm, 
2.1 months for the vinflunine and paclitaxel arms and 1.6 months for the docetaxel arm. 
 
The demographic and baseline disease characteristics of the primary analysis population were well 
balanced between the treatment arms. The median age was 67 years (range: 31 to 88), and 77.1% of 
patients were male. The majority of patients were white (72.1%), 53.9% of patients within the 
chemotherapy arm received vinflunine, 71.4% of patients had at least one poor prognostic risk factor 
and 28.8% had liver metastases at baseline. Baseline ECOG performance status was 0 (45.6%) or 1 
(54.4%). Bladder was the primary tumour site for 71.1% of patients and 25.4% of patients had upper 
tract urothelial carcinoma. There were 24.2% of patients who received only prior platinum-containing 
adjuvant or neoadjuvant therapy and progressed within 12 months. 



22 
 
 

 
The primary efficacy endpoint for IMvigor211 is overall survival (OS). Secondary efficacy endpoints 
evaluated per investigator-assessed Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 are 
objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR). 
Comparisons with respect to OS between the treatment arm and control arm within the IC2/3, IC1/2/3, 
and ITT (Intention-to-treat, i.e. all comers) populations were tested using a hierarchical fixed-sequence 
procedure based on a stratified log-rank test at two-sided level of 5% as follows: step 1) IC2/3 
population; step 2) IC1/2/3 population; step 3) all comers population. OS results for each of steps 2 
and 3 could be formally tested for statistical significance only if the result in the preceding step was 
statistically significant. 
 
The median survival follow-up is 17 months. The primary analysis of study IMvigor211 did not meet 
its primary endpoint of OS. Atezolizumab did not demonstrate a statistically significant survival 
benefit compared to chemotherapy in patients with previously treated, locally advanced or metastatic 
urothelial carcinoma. Per the pre-specified hierarchical testing order, the IC2/3 population was tested 
first, with an OS HR of 0.87 (95% CI: 0.63, 1.21; median OS of 11.1 vs. 10.6 months for atezolizumab 
and chemotherapy respectively). The stratified log-rank p-value was 0.41 and therefore the results are 
considered not statistically significant in this population. As a consequence, no formal tests of 
statistical significance could be performed for OS in the IC1/2/3 or all comer populations, and results 
of those analyses would be considered exploratory. The key results in the all comer population are 
summarised in Table 3. The Kaplan-Meier curve for OS in the all comer population is presented in 
Figure 1. 
 
An exploratory updated survival analysis was performed with a median duration of survival follow up 
of 34 months in the ITT population. The median OS was 8.6 months (95% CI: 7.8, 9.6) in the 
atezolizumab arm and 8.0 months (95% CI: 7.2, 8.6) in the chemotherapy arm with a hazard ratio of 
0.82 (95% CI: 0.71, 0.94). Consistent with the trend observed at primary analysis for 12-month OS 
rates, numerically higher 24-month and 30-month OS rates were observed for patients in the 
atezolizumab arm compared with the chemotherapy arm in the ITT population. The percentage of 
patients alive at 24 months (KM estimate) was 12.7% in the chemotherapy arm and 22.5% in the 
atezolizumab arm; and at 30 months (KM estimate) was 9.8% in the chemotherapy arm and 18.1% in 
the atezolizumab arm. 
 



23 
 
 

Table 3: Summary of efficacy in all comers (IMvigor211) 
 

Efficacy endpoint 
Atezolizumab 

(n = 467) 
Chemotherapy 

(n = 464) 
Primary efficacy endpoint 
OS* 
   No. of deaths (%) 324 (69.4%) 350 (75.4%) 
   Median time to events (months)  8.6 8.0 
   95% CI 7.8, 9.6 7.2, 8.6 

   Stratifiedǂ hazard ratio (95% CI) 0.85 (0.73, 0.99) 

12-month OS (%)** 39.2% 32.4% 
Secondary and exploratory endpoints 
Investigator-assessed PFS (RECIST v1.1) 
   No. of events (%) 407 (87.2%) 410 (88.4%) 
   Median duration of PFS (months) 2.1 4.0 
   95% CI 2.1, 2.2 3.4, 4.2 
   Stratified hazard ratio (95% CI) 1.10 (0.95, 1.26) 
Investigator-assessed ORR (RECIST v1.1) n = 462 n = 461 
   No. of confirmed responders (%) 62 (13.4%) 62 (13.4%) 
   95% CI 10.45, 16.87 10.47, 16.91 
No. of complete response (%) 16 (3.5%) 16 (3.5%) 
No. of partial response (%) 46 (10.0%) 46 (10.0%) 
No. of stable disease (%) 92 (19.9%) 162 (35.1%) 
Investigator-assessed DOR (RECIST v1.1) n = 62 n = 62 
   Median in months *** 21.7 7.4 
   95% CI 13.0, 21.7 6.1, 10.3 

CI = confidence interval; DOR = duration of response; ORR = objective response rate; OS = overall survival; 
PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumours v1.1. 
* An analysis of OS in the all comer population was performed based on the stratified log-rank test and the result 
is provided for descriptive purposes only (p = 0.0378); according to the pre-specified analysis hierarchy, the 
p-value for the OS analysis in the all comer population cannot be considered statistically significant. 
ǂ Stratified by chemotherapy (vinflunine vs. taxane), status on IC (< 5% vs. ≥ 5%), number of prognostic risk 
factors (0 vs. 1-3), and liver metastases (yes vs. no). 
** Based on Kaplan-Meier estimate 
*** Responses were ongoing in 63% of responders in the atezolizumab arm and in 21% of responders in the 
chemotherapy arm. 
 



24 
 
 

Figure 1: Kaplan-Meier curve for overall survival (IMvigor211) 
 

 
 
IMvigor210 (GO29293): Single-arm trial in previously untreated urothelial carcinoma patients who 
are ineligible for cisplatin therapy and in urothelial carcinoma patients previously treated with 
chemotherapy 
 
A phase II, multi-centre, international, two-cohort, single-arm clinical trial, IMvigor210, was 
conducted in patients with locally advanced or metastatic UC (also known as urothelial bladder 
cancer).  
 
The study enrolled a total of 438 patients and had two patient cohorts. Cohort 1 included previously 
untreated patients with locally advanced or metastatic UC who were ineligible or unfit for 
cisplatin-based chemotherapy or had disease progression at least 12 months after treatment with a 
platinum-containing neoadjuvant or adjuvant chemotherapy regimen. Cohort 2 included patients who 
received at least one platinum-based chemotherapy regimen for locally advanced or metastatic UC or 
had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or 
adjuvant chemotherapy regimen. 
 
In Cohort 1, 119 patients were treated with atezolizumab 1,200 mg by intravenous infusion every 
3 weeks until disease progression. The median age was 73 years. Most patients were male (81%), and 
the majority of patients were White (91%).  
 
Cohort 1 included 45 patients (38%) with ECOG performance status of 0, 50 patients (42%) with 
ECOG performance status of 1 and 24 patients (20%) with ECOG performance status of 2, 35 patients 
(29%) with no Bajorin risk factors (ECOG performance status ≥ 2 and visceral metastasis), 66 patients 
(56%) with one Bajorin risk factor and 18 patients (15 %) with two Bajorin risk factors, 84 patients 
(71%) with impaired renal function (glomerular filtration rate [GFR] < 60 mL/min), and 25 patients 
(21%) with liver metastasis. 
 
The primary efficacy endpoint for Cohort 1 was confirmed objective response rate (ORR) as assessed 
by an independent review facility (IRF) using RECIST v1.1.  
 



25 
 
 

The primary analysis was performed when all patients had at least 24 weeks of follow-up. Median 
duration of treatment was 15.0 weeks and median duration of survival follow-up was 8.5 months in all 
comers. Clinically relevant IRF-assessed ORRs per RECIST v1.1 were shown; however, when 
compared to a pre-specified historical control response rate of 10%, statistical significance was not 
reached for the primary endpoint. The confirmed ORRs per IRF-RECIST v1.1 were 21.9% (95% CI: 
9.3, 40.0) in patients with PD-L1 expression ≥ 5%, 18.8% (95% CI: 10.9, 29.0) in patients with PD-L1 
expression ≥ 1%, and 19.3% (95% CI: 12.7, 27.6) in all comers. The median duration of response 
(DOR) was not reached in any PD-L1 expression subgroup or in all comers. OS was not mature with 
an event patient ratio of approximately 40%. Median OS for all patient subgroups (PD-L1 expression 
≥ 5 % and ≥ 1 %) and in all comers was 10.6 months.  
 
An updated analysis was performed with a median duration of survival follow-up of 17.2 months for 
Cohort 1 and is summarised in Table 4. The median DOR was not reached in any PD-L1 expression 
subgroup or in all comers. 
 
Table 4: Summary of updated efficacy (IMvigor210 Cohort 1) 
 

Efficacy endpoint 
PD-L1 

expression of  
≥ 5% in IC 

PD-L1 
expression of  
≥ 1% in IC 

All Comers 

ORR (IRF-assessed; RECIST v1.1) n = 32 n = 80 n = 119 

No. of Responders (%) 9 (28.1%) 19 (23.8%) 27 (22.7%) 
95% CI 13.8, 46.8 15.0, 34.6 15.5, 31.3 

No. of complete response (%) 
95% CI 

4 (12.5%) 
(3.5, 29.0) 

8 (10.0%) 
(4.4, 18.8) 

11 (9.2%) 
(4.7, 15.9) 

No. of partial response (%) 
95% CI 

5 (15.6%) 
(5.3, 32.8) 

11 (13.8%) 
(7.1, 23.3) 

16 (13.4%) 
(7.9, 20.9) 

DOR (IRF-assessed; RECIST v1.1) n = 9 n = 19 n = 27 

Patients with event (%) 3 (33.3%) 5 (26.3%) 8 (29.6%) 
Median (months) (95% CI) NE (11.1, NE) NE (NE) NE (14.1, NE) 

PFS (IRF-assessed; RECIST v1.1) n = 32 n = 80 n = 119 

Patients with event (%) 24 (75.0%) 59 (73.8%) 88 (73.9%) 
Median (months) (95% CI) 4.1 (2.3, 11.8) 2.9 (2.1, 5.4) 2.7 (2.1, 4.2) 

OS n = 32 n = 80 n = 119 

Patients with event (%) 18 (56.3%) 42 (52.5%) 59 (49.6%) 
Median (months) (95% CI) 12.3 (6.0, NE) 14.1 (9.2, NE) 15.9 (10.4, NE) 
1-year OS rate (%) 52.4% 54.8% 57.2% 

CI = confidence interval; DOR=duration of response; IC = tumour-infiltrating immune cells; IRF = independent 
review facility; NE = not estimable; ORR = objective response rate; OS = overall survival; 
PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumours v1.1. 
 
In Cohort 2, the co-primary efficacy endpoints were confirmed ORR as assessed by an IRF using 
RECIST v1.1 and investigator-assessed ORR according to Modified RECIST (mRECIST) criteria. 
There were 310 patients treated with atezolizumab 1,200 mg by intravenous infusion every 3 weeks 
until loss of clinical benefit. The primary analysis of Cohort 2 was performed when all patients had at 
least 24 weeks of follow-up. The study met its co-primary endpoints in Cohort 2, demonstrating 
statistically significant ORRs per IRF-assessed RECIST v1.1 and investigator-assessed mRECIST 
compared to a pre-specified historical control response rate of 10%. 
 
An analysis was also performed with a median duration of survival follow-up of 21.1 months for 
Cohort 2. The confirmed ORRs per IRF-RECIST v1.1 were 28.0% (95% CI: 19.5, 37.9) in patients 



26 
 
 

with PD-L1 expression ≥ 5%, 19.3% (95% CI: 14.2, 25.4) in patients with PD-L1 expression ≥ 1%, 
and 15.8% (95% CI: 11.9, 20.4) in all comers. The confirmed ORR per investigator-assessed 
mRECIST was 29.0% (95% CI: 20.4, 38.9) in patients with PD-L1 expression ≥ 5%, 23.7% (95% CI: 
18.1, 30.1) in patients with PD-L1 expression ≥ 1%, and 19.7% (95% CI: 15.4, 24.6) in all comers. 
The rate of complete response per IRF-RECIST v1.1 in the all comer population was 6.1% (95% CI: 
3.7, 9.4). For Cohort 2, median DOR was not reached in any PD-L1 expression subgroup or in all 
comers, however was reached in patients with PD-L1 expression < 1% (13.3 months; 95% CI 4.2, 
NE). The OS rate at 12 month was 37% in all comers.  
 
IMvigor130 (WO30070): Phase III multi-center, randomised, placebo-controlled study of 
atezolizumab as monotherapy and in combination with platinum-based chemotherapy in patients with 
untreated locally advanced or metastatic urothelial carcinoma 
 
Based on an independent Data Monitoring Committee (iDMC) recommendation following an early 
review of survival data, accrual of patients on the atezolizumab monotherapy treatment arm whose 
tumours have a low PD-L1 expression (less than 5% of immune cells staining positive for PD-L1 by 
immunohistochemistry) was stopped after observing decreased overall survival for this subgroup. The 
iDMC did not recommend any change of therapy for patients who had already been randomised to and 
were receiving treatment in the monotherapy arm. No other changes were recommended. 
 
Non-small cell lung cancer  
 
Second-line treatment of non-small cell lung cancer 
 
OAK (GO28915): Randomised phase III trial in locally advanced or metastatic NSCLC patients 
previously treated with chemotherapy 
 
A phase III, open-label, multi-center, international, randomised study, OAK, was conducted to 
evaluate the efficacy and safety of atezolizumab compared with docetaxel in patients with locally 
advanced or metastatic NSCLC who progressed during or following a platinum-containing regimen. 
This study excluded patients who had a history of autoimmune disease, active or 
corticosteroid-dependent brain metastases, administration of a live, attenuated vaccine within 28 days 
prior to enrolment, administration of systemic immunostimulatory agents within 4 weeks or systemic 
immunosuppressive medicinal product within 2 weeks prior to enrolment. Tumour assessments were 
conducted every 6 weeks for the first 36 weeks, and every 9 weeks thereafter. Tumour specimens were 
evaluated prospectively for PD-L1 expression on tumour cells (TC) and tumour-infiltrating immune 
cells (IC). 
 
A total of 1,225 patients were enrolled and per the analysis plan the first 850 randomised patients were 
included in the primary efficacy analysis. Randomisation was stratified by PD-L1 expression status on 
IC, by the number of prior chemotherapy regimens, and by histology. Patients were randomised (1:1) 
to receive either atezolizumab or docetaxel. 
 
Atezolizumab was administered as a fixed dose of 1,200 mg by intravenous infusion every 3 weeks. 
No dose reduction was allowed. Patients were treated until loss of clinical benefit as assessed by the 
investigator. Docetaxel was administered 75 mg/m2 by intravenous infusion on day 1 of each 3-week 
cycle until disease progression. For all treated patients, the median duration of treatment was 
2.1 months for the docetaxel arm and 3.4 months for the atezolizumab arm.  
 
The demographic and baseline disease characteristics of the primary analysis population were well 
balanced between the treatment arms. The median age was 64 years (range: 33 to 85), and 61% of 
patients were male. The majority of patients were white (70%). Approximately three-quarters of 
patients had non-squamous histology (74%), 10% had known EGFR mutation, 0.2% had known ALK 
rearrangements, 10% had CNS metastases at baseline, and most patients were current or previous 
smokers (82%). Baseline ECOG performance status was 0 (37%) or 1 (63%). Seventy five percent of 
patients received only one prior platinum-based therapeutic regimen. 



27 
 
 

 
The primary efficacy endpoint was OS. The key results of this study with a median survival follow-up 
of 21 months are summarised in Table 5. Kaplan-Meier curves for OS in the ITT population are 
presented in Figure 2. Figure 3 summarises the results of OS in the ITT and PD-L1 subgroups, 
demonstrating OS benefit with atezolizumab in all subgroups, including those with PD-L1 
expression < 1% in TC and IC.  
 
Table 5: Summary of efficacy in the primary analysis population (all comers)* (OAK) 
 

Efficacy endpoint 
Atezolizumab 

(n = 425) 
Docetaxel 
(n = 425) 

Primary efficacy endpoint 
OS  
   No. of deaths (%) 271 (64%) 298 (70%) 
   Median time to events (months)  13.8 9.6 
   95% CI (11.8, 15.7) (8.6, 11.2) 

   Stratifiedǂ hazard ratio (95% CI) 0.73 (0.62, 0.87) 

   p-value** 0.0003 
12-month OS (%)*** 218 (55%) 151 (41%) 
18-month OS (%)*** 157 (40%) 98 (27%) 

Secondary endpoints 
Investigator-assessed PFS (RECIST v1.1) 
   No. of events (%) 380 (89%) 375 (88%) 
   Median duration of PFS (months) 2.8 4.0 
   95% CI (2.6, 3.0) (3.3, 4.2) 
   Stratified hazard ratio (95% CI) 0.95 (0.82, 1.10) 
Investigator-assessed ORR (RECIST v1.1) 
   No. of responders (%) 58 (14%) 57 (13%) 
   95% CI (10.5, 17.3) (10.3, 17.0) 
Investigator-assessed DOR (RECIST v1.1) n = 58 n = 57 
   Median in months 16.3 6.2 
   95% CI (10.0, NE) (4.9, 7.6) 

CI = confidence interval; DOR = duration of response; NE = not estimable; ORR = objective response rate; 
OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid 
Tumours v1.1. 
*The primary analysis population consists of the first 850 randomised patients 
ǂStratified by PD-L1 expression in tumour infiltrating immune cells, the number of prior chemotherapy 
regimens, and histology 
** Based on the stratified log-rank test 
*** Based on Kaplan-Meier estimates 
 



28 
 
 

Figure 2: Kaplan-Meier curve for overall survival in the primary analysis population (all 
comers) (OAK) 
 

 
 
Figure 3: Forest plot of overall survival by PD-L1 expression in the primary analysis population 
(OAK) 
 

 
 

aStratified HR for ITT and TC or IC ≥ 1%. Unstratified HR for other exploratory subgroups. 
 
An improvement in OS was observed with atezolizumab compared to docetaxel in both non-squamous 
NSCLC patients (hazard ratio [HR] of 0.73, 95% CI: 0.60, 0.89; median OS of 15.6 vs. 11.2 months 
for atezolizumab and docetaxel, respectively) and squamous NSCLC patients (HR of 0.73, 
95% CI: 0.54, 0.98; median OS of 8.9 vs. 7.7 months for atezolizumab and docetaxel, respectively). 
The observed OS improvement was consistently demonstrated across subgroups of patients including 
those with brain metastases at baseline (HR of 0.54, 95% CI: 0.31, 0.94; median OS of 20.1 
vs. 11.9 months for atezolizumab and docetaxel respectively) and patients who were never smokers 
(HR of 0.71, 95% CI: 0.47, 1.08; median OS of 16.3 vs. 12.6 months for atezolizumab and docetaxel, 



29 
 
 

respectively). However, patients with EGFR mutations did not show improved OS with atezolizumab 
compared to docetaxel (HR of 1.24, 95% CI: 0.71, 2.18; median OS of 10.5 vs. 16.2 months for 
atezolizumab and docetaxel, respectively).  
 
Prolonged time to deterioration of patient-reported pain in chest as measured by the EORTC 
QLQ-LC13 was observed with atezolizumab compared to docetaxel (HR of 0.71, 95% CI: 0.49, 1.05; 
median not reached in either arm). The time to deterioration in other lung cancer symptoms (i.e. 
cough, dyspnoea, and arm/shoulder pain) as measured by the EORTC QLQ-LC13 was similar 
between atezolizumab and docetaxel. These results should be interpreted with caution due to the open-
label design of the study. 
 
POPLAR (GO28753): Randomised phase II trial in locally advanced or metastatic NSCLC patients 
previously treated with chemotherapy 
 
A phase II, multi-centre, international, randomised, open-label, controlled study, POPLAR, was 
conducted in patients with locally advanced or metastatic NSCLC who progressed during or following 
a platinum-containing regimen, regardless of PD-L1 expression. The primary efficacy outcome was 
overall survival. A total of 287 patients were randomised 1:1 to receive either atezolizumab (1,200 mg 
by intravenous infusion every 3 weeks until loss of clinical benefit) or docetaxel (75 mg/m2 by 
intravenous infusion on day 1 of each 3-week cycle until disease progression). Randomisation was 
stratified by PD-L1 expression status on IC, by the number of prior chemotherapy regimens and by 
histology. An updated analysis with a total of 200 deaths observed and a median survival follow-up of 
22 months showed a median OS of 12.6 months in patients treated with atezolizumab, vs. 9.7 months 
in patients treated with docetaxel (HR of 0.69, 95% CI: 0.52, 0.92). ORR was 15.3% vs. 14.7% and 
median DOR was 18.6 months vs. 7.2 months for atezolizumab vs. docetaxel, respectively.  
 
Triple-negative breast cancer 
 
IMpassion130 (WO29522): Randomised phase III trial in locally advanced or metastatic TNBC 
patients previously untreated for metastatic disease  
 
A phase III, double-blind, two-arm, multi-center, international, randomised, placebo-controlled study, 
IMpassion130, was conducted to evaluate the efficacy and safety of atezolizumab in combination with 
nab-paclitaxel, in patients with unresectable locally advanced or metastatic TNBC who had not 
received prior chemotherapy for metastatic disease. Patients had to be eligible for taxane monotherapy 
(i.e. absence of rapid clinical progression, life-threatening visceral metastases, or need for rapid 
symptom and/or disease control) and were excluded if they had received prior chemotherapy in the 
neoadjuvant or adjuvant setting within the last 12 months, a history of autoimmune disease; 
administration of a live, attenuated vaccine within 4 weeks prior to randomisation, administration of 
systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications 
within 2 weeks prior to randomisation; untreated, symptomatic or corticosteroid-dependent brain 
metastases. Tumour assessments were performed every 8 weeks (± 1 week) for the first 12 months 
after Cycle 1, day 1 and every 12 weeks (± 1 week) thereafter. 
 
A total of 902 patients were enrolled and stratified by presence of liver metastases, prior taxane 
treatment, and by PD-L1 expression status in tumour-infiltrating immune cells (IC) (PD-L1 stained 
tumour-infiltrating immune cells [IC] <1% of tumour area vs. ≥ 1% of the tumour area) assessed by 
the VENTANA PD-L1 (SP142) Assay. 
 
Patients were randomised to receive atezolizumab 840 mg or placebo by intravenous infusions on 
days 1 and 15 of every 28-day cycle, plus nab-paclitaxel (100 mg/m2) administered via intravenous 
infusion on days 1, 8 and 15 of every 28-day cycle. Patients received treatment until radiographic 
disease progression per RECIST v1.1, or unacceptable toxicity. Treatment with atezolizumab could be 
continued when nab-paclitaxel was stopped due to unacceptable toxicity. The median number of 
treatment cycles was 7 for atezolizumab and 6 for nab-paclitaxel in each treatment arm. 
 



30 
 
 

The demographic and baseline disease characteristics of the study population were well balanced 
between the treatment arms. Most patients were women (99.6%), 67.5% were white and 17.8% Asian. 
The median age was 55 years (range: 20-86). Baseline ECOG performance status was 0 (58.4%) 
or 1 (41.3%). Overall, 41% of enrolled patients had PD-L1 expression ≥1%, 27% had liver metastases 
and 7% asymptomatic brain metastases at baseline. Approximately half the patients had received a 
taxane (51%) or anthracycline (54%) in the (neo)adjuvant setting. Patient demographics and baseline 
tumour disease in patients with PD-L1 expression ≥1% were generally representative of the broader 
study population. 
 
The co-primary efficacy endpoints included investigator-assessed progression free survival (PFS) in 
the ITT population and in patients with PD-L1 expression ≥ 1% per RECIST v1.1 as well as overall 
survival (OS) in the ITT population and in patients with PD-L1 expression ≥ 1%. Secondary efficacy 
endpoints included objective response rate (ORR) and duration of response (DOR) per RECIST v1.1.  
 
PFS, ORR and DOR results of IMpassion130 for patients with PD-L1 expression ≥ 1% at the time of 
the final analysis for PFS with a median survival follow up of 13 months are summarised in Table 6 
with Kaplan-Meier curves for PFS in Figure 4.  Patients with PD-L1 expression <1% did not show 
improved PFS when atezolizumab was added to nab-paclitaxel (HR of 0.94, 95% CI 0.78, 1.13). 
 
The final OS analysis was performed in patients with PD-L1 expression ≥ 1% with a median follow up 
of 19.12 months. OS results are presented in Table 6 and Kaplan-Meier curves in Figure 5. Patients 
with PD-L1 expression <1% did not show improved OS when atezolizumab was added to nab-
paclitaxel (HR of 1.02, 95% CI 0.84, 1.24).  
 
Exploratory subgroup analyses were performed in patients with PD-L1 expression ≥ 1%, exploring 
prior (neo)adjuvant treatment, BRCA1/2 mutation and asymptomatic brain metastases at baseline.  
 
In patients who had received prior (neo) adjuvant treatment (n=242), the hazard ratio for primary 
(final) PFS was 0.79 and 0.77 for final OS while in patients who had not received prior (neo)adjuvant 
treatment (n=127), the hazard ratio for primary (final) PFS was 0.44 and 0.54 for final OS.  
 
In the IMpassion130 study, of the 614 patients tested, 89 (15%) carried pathogenic BRCA1/2 
mutations. From the PD-L1+/BRCA1/2 mutant subgroup, 19 patients received atezolizumab plus nab-
paclitaxel and 26 placebo plus nab-paclitaxel. Based on exploratory analysis and acknowledging the 
small sample size, the presence of BRCA1/2 mutation does not seem to impact the PFS clinical benefit 
of atezolizumab and nab-paclitaxel. 
 
There was no evidence of efficacy in patients with asymptomatic brain metastases at baseline, 
although the number of patients treated was small; the median PFS was 2.2 months in the 
atezolizumab plus nab-paclitaxel arm (n=15) compared to 5.6 months in the placebo plus nab-
paclitaxel arm (n=11) (HR 1.40; 95% CI 0.57, 3.44).  
 



31 
 
 

Table 6 - Summary of efficacy in patients with PD-L1 expression ≥1% (IMpassion130) 
 

Key efficacy endpoints Atezolizumab + nab-paclitaxel Placebo + nab-paclitaxel 

Primary efficacy endpoints n=185 n=184 

Investigator-assessed PFS (RECIST v1.1) – Primary analysis3   
No. of events (%) 138 (74.6%) 157 (85.3%) 
Median duration of PFS (months) 7.5 5.0 
95% CI (6.7, 9.2) (3.8, 5.6) 
 Stratified hazard ratio‡ (95% CI) 0.62 (0.49, 0.78) 
 p-value1  <0.0001 
 12-month PFS (%) 29.1 16.4 

Investigator-assessed PFS (RECIST v1.1) – Updated exploratory analysis4 
No. of events (%) 149 (80.5%) 163 (88.6%) 
Median duration of PFS (months) 7.5 5.3 
95% CI (6.7, 9.2) (3.8, 5.6) 
 Stratified hazard ratio‡ (95% CI) 0.63 (0.50-0.80) 
 p-value1  <0.0001 
 12-month PFS (%) 30.3 17.3 

OS 1,2,5  
  

No. of deaths (%) 120 (64.9%) 139 (75.5%) 
Median time to events (months) 25.4 17.9 
95% CI  (19.6, 30.7)  (13.6, 20.3) 
Stratified hazard ratio‡ (95% CI)  0.67 (0.53, 0.86) 

Secondary and exploratory endpoints 

Investigator-assessed ORR (RECIST 1.1)3 n=185 n=183 
No. of responders (%) 109 (58.9%) 78 (42.6%) 
95% CI (51.5, 66.1) (35.4, 50.1) 
 No. of complete response (%) 19 (10.3%) 2 (1.1%) 
 No. of partial response (%) 90 (48.6%) 76 (41.5%) 
 No. of stable disease 38 (20.5%) 49 (26.8%) 

Investigator-assessed DOR3 n=109 n=78 
Median in months 8.5 5.5 
95% CI (7.3, 9.7) (3.7, 7.1) 
1. Based on the stratified log-rank test. 
2. OS comparisons between treatment arms in patients with PD-L1 expression ≥1% were not formally tested, as per 

the pre-specified analysis hierarchy. 
3. Per final analysis for PFS, ORR, DOR and first interim analysis for OS at clinical cut off 17th April 2018 
4. Per exploratory PFS analysis at clinical cut off January 2nd 2019 
5. Per final analysis for OS at clinical cut off April 14th 2020 
‡ Stratified by presence of liver metastases, and by prior taxane treatment. 
PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumours v1.1.; CI=confidence 
interval; ORR=objective response rate; DOR=duration of response; OS=overall survival, NE=not estimable 
 



32 
 
 

Figure 4: Kaplan-Meier Curve for Progression Free Survival in patients with PD-L1 
expression ≥ 1% (IMpassion130) 
 

 
 
Figure 5: Kaplan-Meier Curve for Overall Survival in patients with PD-L1 expression ≥ 1% 
(IMpassion130) 
 

 
 
The time to deterioration (a sustained ≥ 10-point decline from baseline score) of patient-reported 
global health status/health-related quality of life as measured by the EORTC QLQ-C30 was similar in 
each treatment group indicating that all patients maintained their baseline HRQoL for a comparable 
duration of time. 
 



33 
 
 

Efficacy in elderly patients 
 
No overall differences in efficacy were observed between patients ≥ 65 years of age and younger 
patients receiving atezolizumab monotherapy. Data for patients ≥75 years of age are too limited to 
draw conclusions on this population. 
 
Paediatric population 
 
An early phase, multi-centre open-label study was conducted in paediatric (<18, n=69) and young 
adult patients (18-30 years, n=18) with relapsed or progressive solid tumours as well as with 
Hodgkin’s and non-Hodgkin’s lymphoma, to evaluate the safety and pharmacokinetics of 
atezolizumab. Patients were treated with 15 mg/kg atezolizumab IV every 3 weeks (see section 5.2).  
 
5.2 Pharmacokinetic properties 
 
Exposure to atezolizumab increased dose proportionally over the dose range 1 mg/kg to 20 mg/kg 
including the fixed dose 1,200 mg administered every 3 weeks. A population analysis that included 
472 patients described atezolizumab pharmacokinetics for the dose range: 1 to 20 mg/kg with a linear 
two-compartment disposition model with first-order elimination. The pharmacokinetic properties of 
atezolizumab 840 mg administered every 2 weeks and atezolizumab 1,200 mg administered every 
3 weeks are comparable. A population pharmacokinetic analysis suggests that steady-state is obtained 
after 6 to 9 weeks after multiple doses. The maximum systemic accumulation ratio across dosing 
regimens is 3.3. 
 
Absorption 
 
Atezolizumab is administered as an intravenous infusion. There have been no studies performed with 
other routes of administration. 
 
Distribution 
 
A population pharmacokinetic analysis indicates that central compartment volume of distribution is 
3.28 L and volume at steady-state is 6.91 L in the typical patient. 
 
Biotransformation 
 
The metabolism of atezolizumab has not been directly studied. Antibodies are cleared principally by 
catabolism. 
 
Elimination 
 
A population pharmacokinetic analysis indicates that the clearance of atezolizumab is 0.200 L/day and 
the typical terminal elimination half-life is 27 days. 
 
Special populations 
 
Based on population PK and exposure-response analyses age (21-89 years), region, ethnicity, renal 
impairment, mild hepatic impairment, level of PD-L1 expression, or ECOG performance status have 
no effect on atezolizumab pharmacokinetics. Body weight, gender, positive ADA status, albumin 
levels and tumour burden have a statistically significant, but not clinically relevant effect on 
atezolizumab pharmacokinetics. No dose adjustments are recommended. 
 



34 
 
 

Elderly 
 
No dedicated studies of atezolizumab have been conducted in elderly patients. The effect of age on the 
pharmacokinetics of atezolizumab was assessed in a population pharmacokinetic analysis. Age was 
not identified as a significant covariate influencing atezolizumab pharmacokinetics based on patients 
of age range of 21-89 years (n=472), and median of 62 years of age. No clinically important difference 
was observed in the pharmacokinetics of atezolizumab among patients < 65 years (n=274), patients 
between 65−75 years (n=152) and patients > 75 years (n=46) (see section 4.2). 
 
Paediatric population 
 
The pharmacokinetic results from one early-phase, multi-centre open-label study that was conducted 
in paediatric (<18 years, n=69) and young adult patients (18-30 years, n=18), show that the clearance 
and volume of distribution of atezolizumab were comparable between paediatric patients receiving 
15 mg/kg and young adult patients receiving 1,200 mg of atezolizumab every 3 weeks when 
normalized by body weight, with exposure trending lower in paediatric patients as body weight 
decreased. These differences were not associated with a decrease in atezolizumab concentrations 
below the therapeutic target exposure. Data for children <2 years is limited thus no definitive 
conclusions can be made.  
 
Renal impairment 
 
No dedicated studies of atezolizumab have been conducted in patients with renal impairment. In the 
population pharmacokinetic analysis, no clinically important differences in the clearance of 
atezolizumab were found in patients with mild (estimated glomerular filtration rate [eGFR] 60 to 
89 mL/min/1.73 m2; n=208) or, moderate (eGFR 30 to 59 mL/min/1.73 m2; n=116) renal impairment 
compared to patients with normal (eGFR greater than or equal to 90 mL/min/1.73 m2; n=140) renal 
function. Only a few patients had severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2; n=8) (see 
section 4.2). The effect of severe renal impairment on the pharmacokinetics of atezolizumab is 
unknown. 
 
Hepatic impairment 
 
No dedicated studies of atezolizumab have been conducted in patients with hepatic impairment. In the 
population pharmacokinetic analysis, there were no clinically important differences in the clearance of 
atezolizumab observed in patients with mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or 
bilirubin > 1.0 × to 1.5 × ULN and any AST) or moderate hepatic impairment (bilirubin > 1.5 to 3x 
ULN and any AST) in comparison to patients with normal hepatic function (bilirubin ≤ ULN and AST 
≤ ULN). No data are available in patients with severe hepatic impairment (bilirubin >3 X ULN and 
any AST). Hepatic impairment was defined by the National Cancer Institute-Organ Dysfunction 
Working Group (NCI-ODWG) criteria of hepatic dysfunction (see section 4.2). The effect of severe 
hepatic impairment (bilirubin > 3 × ULN and any AST) on the pharmacokinetics of atezolizumab is 
unknown. 
 
5.3 Preclinical safety data 
 
Carcinogenicity 
 
Carcinogenicity studies have not been performed to establish the carcinogenic potential of 
atezolizumab. 
 



35 
 
 

Mutagenicity 
 
Mutagenicity studies have not been performed to establish the mutagenic potential of atezolizumab. 
However, monoclonal antibodies are not expected to alter DNA or chromosomes.  
 
Fertility 
 
No fertility studies have been conducted with atezolizumab; however assessment of the cynomolgus 
monkey male and female reproductive organs was included in the chronic toxicity study. Weekly 
administration of atezolizumab to female monkeys at an estimated AUC approximately 6 times the 
AUC in patients receiving the recommended dose caused an irregular menstrual cycle pattern and a 
lack of newly formed corpora lutea in the ovaries which were reversible. There was no effect on the 
male reproductive organs.  
 
Teratogenicity  
 
No reproductive or teratogenicity studies in animals have been conducted with atezolizumab. Animal 
studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to immune-related 
rejection of the developing foetus resulting in foetal death. Administration of atezolizumab could 
cause foetal harm, including embryo-foetal lethality. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
L-histidine 
Glacial acetic acid 
Sucrose 
Polysorbate 20 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products except those mentioned in section 6.6. 
 
6.3 Shelf life 
 
Unopened vial 
 
3 years. 
 
Diluted solution 
 
Chemical and physical in-use stability has been demonstrated for up to 24 hours at ≤ 30 °C and for up 
to 30 days at 2 C to 8 C from the time of preparation.  
 
From a microbiological point of view, the prepared solution for infusion should be used immediately. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user and would normally not be longer than 24 hours at 2 °C to 8 °C or 8 hours at ambient temperature 
(≤ 25 °C) unless dilution has taken place in controlled and validated aseptic conditions. 
 



36 
 
 

6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C – 8 °C). 
 
Do not freeze. 
 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Type I glass vial with a butyl rubber stopper and an aluminium seal with a plastic, grey flip-off cap 
containing 14 mL of concentrate for solution for infusion.  
 
Pack of one vial. 
 
6.6 Special precautions for disposal and other handling 
 
Tecentriq does not contain any antimicrobial preservative or bacteriostatic agents and should be 
prepared by a healthcare professional using aseptic technique to ensure the sterility of prepared 
solutions. 
 
Aseptic preparation, handling and storage 
 
Aseptic handling must be ensured when preparing the infusion. Preparation should be:  
• performed under aseptic conditions by trained personnel in accordance with good practice rules 

especially with respect to the aseptic preparation of parenteral products.  
• prepared in a laminar flow hood or biological safety cabinet using standard precautions for the 

safe handling of intravenous agents.  
• followed by adequate storage of the prepared solution for intravenous infusion to ensure 

maintenance of the aseptic conditions. 
 
Do not shake. 
 
Instructions for dilution 
 
For the recommended dose of 840 mg: fourteen mL of Tecentriq concentrate should be withdrawn 
from the vial and diluted into a polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or 
polypropylene (PP) infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection.  
 
For the recommended dose of 1680 mg: twenty-eight mL of Tecentriq concentrate should be 
withdrawn from two vials of Tecentriq 840 mg and diluted into a polyvinyl chloride (PVC), polyolefin 
(PO), polyethylene (PE), or polypropylene (PP) infusion bag containing sodium chloride 9 mg/mL 
(0.9%) solution for injection. 
 
After dilution, the final concentration of the diluted solution should be between 3.2 and 16.8 mg/mL. 
 
The bag should be gently inverted to mix the solution in order to avoid foaming. Once the infusion is 
prepared it should be administered immediately (see section 6.3). 
 
Parenteral medicinal products should be inspected visually for particulates and discolouration prior to 
administration. If particulates or discoloration are observed, the solution should not be used.  
 
No incompatibilities have been observed between Tecentriq and intravenous bags with 
product-contacting surfaces of polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or 



37 
 
 

polypropylene (PP). In addition, no incompatibilities have been observed with in-line filter membranes 
composed of polyethersulfone or polysulfone, and infusion sets and other infusion aids composed of 
PVC, PE, polybutadiene, or polyetherurethane. The use of in-line filter membranes is optional. 
 
Do not co-administer other medicinal products through the same infusion line. 
 
Disposal  
 
The release of Tecentriq in the environment should be minimised. Any unused medicinal product or 
waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1220/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 September 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


38 
 
 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tecentriq 1,200 mg concentrate for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One 20 mL vial of concentrate contains 1,200 mg atezolizumab*. 
 
After dilution (see section 6.6), the final concentration of the diluted solution should be between 3.2 
and 16.8 mg/mL. 
 
*Atezolizumab is an Fc-engineered, humanised IgG1 anti-programmed death-ligand 1 (PD-L1) 
monoclonal antibody produced in Chinese hamster ovary cells by recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
 
Clear, colourless to slightly yellowish liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Urothelial carcinoma  
 
Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or 
metastatic urothelial carcinoma (UC): 
• after prior platinum-containing chemotherapy, or 
• who are considered cisplatin ineligible, and whose tumours have a PD-L1 expression ≥ 5% (see 

section 5.1). 
 
Non-small cell lung cancer   
 
Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated for the first-line 
treatment of adult patients with metastatic non-squamous non-small cell lung cancer (NSCLC). In 
patients with EGFR mutant or ALK-positive NSCLC, Tecentriq, in combination with bevacizumab, 
paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies (see section 
5.1). 
 
Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or 
metastatic NSCLC after prior chemotherapy. Patients with EGFR mutant or ALK-positive NSCLC 
should also have received targeted therapies before receiving Tecentriq (see section 5.1). 
 



39 
 
 

Tecentriq, in combination with nab-paclitaxel and carboplatin, is indicated for the first-line treatment 
of adult patients with metastatic non-squamous NSCLC who do not have EGFR mutant or 
ALK-positive NSCLC (see section 5.1). 
 
Small cell lung cancer  
 
Tecentriq, in combination with carboplatin and etoposide, is indicated for the first-line treatment of 
adult patients with extensive-stage small cell lung cancer (ES-SCLC) (see section 5.1).  
 
Hepatocellular carcinoma 
 
Tecentriq, in combination with bevacizumab, is indicated for the treatment of adult patients with 
advanced or unresectable hepatocellular carcinoma (HCC) who have not received prior systemic 
therapy (see section 5.1). 
 
4.2 Posology and method of administration 
 
Tecentriq must be initiated and supervised by physicians experienced in the treatment of cancer. 
 
PD-L1 testing for patients with UC 
 
Patients with previously untreated UC should be selected for treatment based on the tumour expression 
of PD-L1 confirmed by a validated test (see section 5.1). 
 
Posology 
 
Tecentriq monotherapy 
 
The recommended dose of Tecentriq is 1,200 mg administered intravenously every three weeks.  
 
Tecentriq in combination therapy 
 
Please also refer to the full prescribing information for the combination products (see also section 5.1). 
 
1L non-squamous NSCLC 
 
Tecentriq in combination with bevacizumab, paclitaxel, and carboplatin 
 
During the induction phase, the recommended dose of Tecentriq is 1,200 mg administered by 
intravenous infusion, followed by bevacizumab, paclitaxel, and then carboplatin every three weeks for 
four or six cycles. 
 
The induction phase is followed by a maintenance phase without chemotherapy in which 1,200 mg 
Tecentriq followed by bevacizumab, is administered by intravenous infusion every three weeks. 
 
Tecentriq in combination with nab-paclitaxel and carboplatin 
 
During the induction phase, the recommended dose of Tecentriq is 1,200 mg administered by 
intravenous infusion, followed by nab-paclitaxel and carboplatin every three weeks for four or six 
cycles. For each 21-day cycle, Tecentriq, nab-paclitaxel, and carboplatin are administered on day 1. In 
addition, nab-paclitaxel is administered on days 8 and 15. 
 
The induction phase is followed by a maintenance phase without chemotherapy in which 1,200 mg 
Tecentriq is administered by intravenous infusion every three weeks.  
 



40 
 
 

1L ES-SCLC 
 
Tecentriq in combination with carboplatin and etoposide 
 
During the induction phase, the recommended dose of Tecentriq is 1,200 mg administered by 
intravenous infusion followed by carboplatin, and then etoposide administered by intravenous infusion 
on day 1. Etoposide is also administered by intravenous infusion on days 2 and 3. This regimen is 
administered every three weeks for four cycles. 
 
The induction phase is followed by a maintenance phase without chemotherapy in which 1,200 mg 
Tecentriq is administered by intravenous infusion every three weeks. 
 
HCC 
 
Tecentriq in combination with bevacizumab  
 
The recommended dose of Tecentriq is 1,200 mg followed by bevacizumab 15 mg/kg of body weight, 
administered by intravenous infusion every three weeks. 
 
Duration of treatment 
 
It is recommended that patients are treated with Tecentriq until loss of clinical benefit (see section 5.1) 
or unmanageable toxicity. 
 
For ES-SCLC and for first-line NSCLC, in patients given Tecentriq in combination with carboplatin 
and nab-paclitaxel, it is recommended that patients are treated with Tecentriq until disease progression 
or unmanageable toxicity. Treatment beyond disease progression may be considered at the discretion 
of the physician (see section 5.1). 
 
Delayed or missed doses 
 
If a planned dose of Tecentriq is missed, it should be administered as soon as possible. The schedule 
of administration must be adjusted to maintain a 3-week interval between doses.  
  
Dose modifications during treatment 
 
Dose reductions of Tecentriq are not recommended. 
 



41 
 
 

Dose delay or discontinuation (see also sections 4.4 and 4.8) 
 
Table 1: Dose modification advice for Tecentriq 
 

Immune related adverse 
reaction 

Severity Treatment modification 

Pneumonitis 
 

Grade 2 Withhold Tecentriq 
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks, and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

 Grade 3 or 4 Permanently discontinue Tecentriq 
Hepatitis in patients without 
HCC 
 
 
 

Grade 2: 
(ALT or AST > 3 to 5 x upper limit of 
normal [ULN] 
 
or 
 
blood bilirubin > 1.5 to 3 x ULN) 
 

Withhold Tecentriq 
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 3 or 4: 
(ALT or AST > 5 x ULN 
 
or 
 
blood bilirubin > 3 x ULN) 

Permanently discontinue Tecentriq 

Hepatitis in patients with 
HCC 

If AST/ALT is within normal limits at 
baseline and increases to >3x to ≤10x 
ULN  
 
or 
 
If AST/ALT is >1 to ≤3x ULN at 
baseline and increases to >5x to ≤10x 
ULN 
 
or 
 
If AST/ALT is >3x to ≤5x ULN at 
baseline and increases to  >8x to ≤10x 
ULN 

Withhold Tecentriq  
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

If AST/ALT increases to >10x ULN  
 
or  
 
total bilirubin increases to >3x ULN 

Permanently discontinue Tecentriq 

Colitis 
 

Grade 2 or 3 Diarrhoea (increase of ≥ 4 
stools/day over baseline) 
 
or 
 
Symptomatic Colitis 

Withhold Tecentriq  
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 4 Diarrhoea or Colitis (life 
threatening; urgent intervention 
indicated) 

Permanently discontinue Tecentriq 



42 
 
 

Immune related adverse 
reaction 

Severity Treatment modification 

Hypothyroidism or 
hyperthyroidism 
 

Symptomatic Withhold Tecentriq 
 
Hypothyroidism: 
Treatment may be resumed when 
symptoms are controlled by thyroid 
replacement therapy and TSH levels 
are decreasing 
 
Hyperthyroidism: 
Treatment may be resumed when 
symptoms are controlled by anti-
thyroid medicinal product and 
thyroid function is improving 

Adrenal insufficiency 
 

Symptomatic 
 

Withhold Tecentriq 
 
Treatment may be resumed when the 
symptoms improve to Grade 0 or 
Grade 1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day and patient is stable on 
replacement therapy 

Hypophysitis Grade 2 or 3 Withhold Tecentriq 
 
Treatment may be resumed when the 
symptoms improve to Grade 0 or 
Grade 1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day and patient is stable on 
replacement therapy 

Grade 4 Permanently discontinue Tecentriq 
Type 1 diabetes mellitus Grade 3 or 4 hyperglycaemia (fasting 

glucose > 250 mg/dL or 
13.9 mmol/L) 
 
 

Withhold Tecentriq 
 
Treatment may be resumed when 
metabolic control is achieved on 
insulin replacement therapy 

Infusion-related reactions 
 

Grade 1 or 2 Reduce infusion rate or interrupt. 
Treatment may be resumed when the 
event is resolved 

Grade 3 or 4 Permanently discontinue Tecentriq 
Rash 
 

Grade 3 Withhold Tecentriq  
 
Treatment may be resumed when 
rash is resolved and corticosteroids 
have been reduced to ≤ 10 mg 
prednisone or equivalent per day 

Grade 4 Permanently discontinue Tecentriq 
Myasthenic 
syndrome/myasthenia 
gravis, Guillain-Barré 
syndrome and 
Meningoencephalitis 
 

All Grades Permanently discontinue Tecentriq 



43 
 
 

Immune related adverse 
reaction 

Severity Treatment modification 

Pancreatitis Grade 3 or 4 serum amylase or lipase 
levels increased (> 2 x ULN) 
or Grade 2 or 3 pancreatitis 
 

Withhold Tecentriq  
 
Treatment may be resumed when 
serum amylase and lipase levels 
improve to Grade 0 or Grade 1 
within 12 weeks, or symptoms of 
pancreatitis have resolved, and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 4 or any grade of recurrent 
pancreatitis 

Permanently discontinue Tecentriq 

Myocarditis Grade 2 Withhold Tecentriq  
 
Treatment may be resumed when the 
symptoms improve to Grade 0 or 
Grade 1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 3 or 4 Permanently discontinue Tecentriq 
Nephritis Grade 2: 

(creatinine level > 1.5 to 3.0 x baseline 
or > 1.5 to 3.0 x ULN) 

Withhold Tecentriq 
 
Treatment may be resumed when the 
event improves to Grade 0 or Grade 
1 within 12 weeks and 
corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent 
per day 

Grade 3 or 4: 
(creatinine level > 3.0 x baseline or > 
3.0 x ULN) 

Permanently discontinue Tecentriq 
 

Myositis Grade 2 or 3 Withhold Tecentriq 
Grade 4 or grade 3 recurrent myositis Permanently discontinue Tecentriq 

Other immune-related 
adverse reactions 

Grade 2 or Grade 3 Withhold until adverse reactions 
recovers to Grade 0-1 within 12 
weeks, and corticosteroids have been 
reduced to ≤ 10 mg prednisone or 
equivalent per day. 

Grade 4 or recurrent Grade 3 Permanently discontinue Tecentriq 
(except endocrinopathies controlled 
with replacement hormones) 

Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for 
Adverse Event Version 4.0 (NCI-CTCAE v.4.).  
 
Special populations 
 
Paediatric population  
 
The safety and efficacy of Tecentriq in children and adolescents aged below 18 years have not been 
established. Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation 
on a posology can be made. 
 
Elderly 
 
Based on a population pharmacokinetic analysis, no dose adjustment of Tecentriq is required in 
patients ≥ 65 years of age (see sections 4.8 and 5.1).  
 



44 
 
 

Asian patients 
 
Due to increased haematologic toxicities observed in Asian patients in IMpower150, it is 
recommended that the starting dose of paclitaxel should be 175 mg/m2 every three weeks. 
 
Renal impairment 
 
Based on a population pharmacokinetic analysis, no dose adjustment is required in patients with mild 
or moderate renal impairment (see section 5.2). Data from patients with severe renal impairment are 
too limited to draw conclusions on this population. 
 
Hepatic impairment 
 
Based on a population pharmacokinetic analysis, no dose adjustment is required for patients with mild 
or moderate hepatic impairment. Tecentriq has not been studied in patients with severe hepatic 
impairment (see section 5.2). 
 
Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 
 
Patients with ECOG performance status ≥ 2 were excluded from the clinical trials in NSCLC, ES-
SCLC, 2nd line UC and HCC (see sections 4.4 and 5.1). 
 
Method of administration  
 
Tecentriq is for intravenous use. The infusions must not be administered as an intravenous push or 
bolus. 
 
The initial dose of Tecentriq must be administered over 60 minutes. If the first infusion is well 
tolerated, all subsequent infusions may be administered over 30 minutes. 
 
For instructions on dilution and handling of the medicinal product before administration, see 
section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to atezolizumab or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the trade name and the batch 
number of the administered product should be clearly recorded in the patient file. 
 
Immune-related adverse reactions 
 
Most immune-related adverse reactions occurring during treatment with atezolizumab were reversible 
with interruptions of atezolizumab and initiation of corticosteroids and/or supportive care. 
Immune-related adverse reactions affecting more than one body system have been observed. 
Immune-related adverse reactions with atezolizumab may occur after the last dose of atezolizumab. 
 
For suspected immune-related adverse reactions, thorough evaluation to confirm aetiology or exclude 
other causes should be performed. Based on the severity of the adverse reaction, atezolizumab should 
be withheld and corticosteroids administered. Upon improvement to Grade ≤ 1, corticosteroid should 
be tapered over ≥ 1 month. Based on limited data from clinical studies in patients whose 



45 
 
 

immune-related adverse reactions could not be controlled with systemic corticosteroid use, 
administration of other systemic immunosuppressants may be considered. 
 
Atezolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction 
that recurs and for any Grade 4 immune-related adverse reactions, except for endocrinopathies that are 
controlled with replacement hormones (see sections 4.2 and 4.8). 
 
Immune-related pneumonitis  
 
Cases of pneumonitis, including fatal cases, have been observed in clinical trials with atezolizumab 
(see section 4.8). Patients should be monitored for signs and symptoms of pneumonitis and causes 
other than immune-related pneumonitis should be ruled out. 
 
Treatment with atezolizumab should be withheld for Grade 2 pneumonitis, and 1 to 2 mg/kg/day 
prednisone or equivalent should be started. If symptoms improve to ≤ Grade 1, corticosteroids should 
be tapered over ≥ 1 month. Treatment with atezolizumab may be resumed if the event improves to 
≤ Grade 1 within 12 weeks, and corticosteroids have been reduced to ≤ 10 mg prednisone or 
equivalent per day. Treatment with atezolizumab must be permanently discontinued for Grade 3 or 4 
pneumonitis. 
 
Immune-related hepatitis  
 
Cases of hepatitis, some leading to fatal outcomes have been observed in clinical trials with 
atezolizumab (see section 4.8). Patients should be monitored for signs and symptoms of hepatitis. 
 
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin should be monitored 
prior to initiation of treatment, periodically during treatment with atezolizumab and as indicated based 
on clinical evaluation. 
 
For patients without HCC, treatment with atezolizumab should be withheld if Grade 2 event (ALT or 
AST > 3 to 5 x ULN or blood bilirubin > 1.5 to 3 x ULN) persists for more than 5 to 7 days, and 1 to 
2 mg/kg/day of prednisone or equivalent should be started. If the event improves to ≤ Grade 1, 
corticosteroids should be tapered over ≥ 1 month.  
 
Treatment with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued for Grade 3 or Grade 4 events (ALT or AST 
> 5.0 x ULN or blood bilirubin > 3 x ULN). 
 
For patients with HCC, treatment with atezolizumab should be withheld if ALT or AST increases to 
> 3 to ≤10 x ULN from normal limits at baseline, or > 5 to ≤10 x ULN from > 1 ULN to ≤3 x ULN at 
baseline, or > 8 to ≤10 x ULN from > 3 ULN to ≤5 x ULN at baseline, and persists for more than 5 to 
7 days, and 1 to 2 mg/kg/day of prednisone or equivalent should be started. If the event improves to 
≤ Grade 1, corticosteroids should be tapered over ≥ 1 month.  
 
Treatment with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued if ALT or AST increases to  > 10 x ULN or total 
bilirubin increases > 3 x ULN). 
 
Immune-related colitis 
 
Cases of diarrhoea or colitis have been observed in clinical trials with atezolizumab (see section 4.8). 
Patients should be monitored for signs and symptoms of colitis.  
 



46 
 
 

Treatment with atezolizumab should be withheld for Grade 2 or 3 diarrhoea (increase of ≥ 4 stools/day 
over baseline) or colitis (symptomatic). For Grade 2 diarrhoea or colitis, if symptoms persist > 5 days 
or recur, treatment with 1 to 2 mg/kg/day prednisone or equivalent should be started. For 
Grade 3 diarrhoea or colitis, treatment with intravenous corticosteroids (1 to 2 mg/kg/day 
methylprednisolone or equivalent) should be started. Once symptoms improve, treatment with 
1 to 2 mg/kg/day of prednisone or equivalent should be started. If symptoms improve to ≤ Grade 1, 
corticosteroids should be tapered over ≥ 1 month. Treatment with atezolizumab may be resumed if the 
event improves to ≤ Grade 1 within 12 weeks and corticosteroids have been reduced to ≤ 10 mg 
prednisone or equivalent per day. Treatment with atezolizumab must be permanently discontinued for 
Grade 4 (life threatening; urgent intervention indicated) diarrhoea or colitis. 
 
Immune-related endocrinopathies  
 
Hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis and type 1 diabetes mellitus, 
including diabetic ketoacidosis have been observed in clinical trials with atezolizumab (see section 
4.8).  
 
Patients should be monitored for clinical signs and symptoms of endocrinopathies. Thyroid function 
should be monitored prior to and periodically during treatment with atezolizumab. Appropriate 
management of patients with abnormal thyroid function tests at baseline should be considered. 
 
Asymptomatic patients with abnormal thyroid function tests can receive atezolizumab. For 
symptomatic hypothyroidism, atezolizumab should be withheld and thyroid hormone replacement 
should be initiated as needed. Isolated hypothyroidism may be managed with replacement therapy and 
without corticosteroids. For symptomatic hyperthyroidism, atezolizumab should be withheld and an 
anti-thyroid medicinal product should be initiated as needed. Treatment with atezolizumab may be 
resumed when symptoms are controlled and thyroid function is improving. 
 
For symptomatic adrenal insufficiency, atezolizumab should be withheld and treatment with 
intravenous corticosteroids (1 to 2 mg/kg/day methylprednisolone or equivalent) should be started. 
Once symptoms improve, treatment with 1 to 2 mg/kg/day of prednisone or equivalent should follow. 
If symptoms improve to ≤ Grade 1, corticosteroids should be tapered over ≥ 1 month. Treatment may 
be resumed if the event improves to ≤ Grade 1 within 12 weeks and corticosteroids have been reduced 
to ≤ 10 mg prednisone or equivalent per day and the patient is stable on replacement therapy (if 
required). 
 
For Grade 2 or Grade 3 hypophysitis, atezolizumab should be withheld and treatment with intravenous 
corticosteroids (1 to 2 mg/kg/day methylprednisolone or equivalent) should be started, and hormone 
replacement should be initiated as needed. Once symptoms improve, treatment with 1 to 2 mg/kg/day 
of prednisone or equivalent should follow. If symptoms improve to ≤ Grade 1, corticosteroids should 
be tapered over ≥ 1 month. Treatment may be resumed if the event improves to ≤ Grade 1 within 
12 weeks and corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day and the 
patient is stable on replacement therapy (if required). Treatment with atezolizumab should be 
permanently discontinued for Grade 4 hypophysitis. 
 
Treatment with insulin should be initiated for type 1 diabetes mellitus. For ≥ Grade 3 hyperglycaemia 
(fasting glucose > 250 mg/dL or 13.9 mmol/L), atezolizumab should be withheld. Treatment with 
atezolizumab may be resumed if metabolic control is achieved on insulin replacement therapy. 
 
Immune-related meningoencephalitis  
 
Meningoencephalitis has been observed in clinical trials with atezolizumab (see section 4.8). Patients 
should be monitored for clinical signs and symptoms of meningitis or encephalitis. 
 
Treatment with atezolizumab must be permanently discontinued for any grade of meningitis or 
encephalitis. Treatment with intravenous corticosteroids (1 to 2 mg/kg/day methylprednisolone or 



47 
 
 

equivalent) should be started. Once symptoms improve, treatment with 1 to 2 mg/kg/day of prednisone 
or equivalent should follow.  
 
Immune-related neuropathies 
 
Myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome, which may be life threatening, 
were observed in patients receiving atezolizumab. Patients should be monitored for symptoms of 
motor and sensory neuropathy.  
 
Treatment with atezolizumab must be permanently discontinued for any grade of myasthenic 
syndrome / myasthenia gravis or Guillain-Barré syndrome. Initiation of systemic corticosteroids (at a 
dose of 1 to 2 mg/kg/day of prednisone or equivalent) should be considered. 
 
Immune-related pancreatitis 
 
Pancreatitis, including increases in serum amylase and lipase levels, has been observed in clinical 
trials with atezolizumab (see section 4.8). Patients should be closely monitored for signs and 
symptoms that are suggestive of acute pancreatitis. 
 
Treatment with atezolizumab should be withheld for ≥ Grade 3 serum amylase or lipase levels 
increased (> 2 x ULN), or Grade 2 or 3 pancreatitis, and treatment with intravenous corticosteroids  
(1 to 2 mg/kg/day methylprednisolone or equivalent) should be started. Once symptoms improve, 
treatment with 1 to 2 mg/kg/day of prednisone or equivalent should follow. Treatment with 
atezolizumab may be resumed when serum amylase and lipase levels improve to ≤ Grade 1 within 
12 weeks, or symptoms of pancreatitis have resolved, and corticosteroids have been reduced to 
≤ 10 mg prednisone or equivalent per day. Treatment with atezolizumab should be permanently 
discontinued for Grade 4, or any grade of recurrent pancreatitis. 
 
Immune-related myocarditis 
 
Myocarditis has been observed in clinical trials with atezolizumab (see section 4.8). Patients should be 
monitored for signs and symptoms of myocarditis.  
 
Treatment with atezolizumab should be withheld for Grade 2 myocarditis, and treatment with systemic 
corticosteroids at a dose of 1 to 2mg/kg/day of prednisone or equivalent should be started. Treatment 
with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks, and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued for Grade 3 or 4 myocarditis. 
 
Immune-related nephritis 
 
Nephritis has been observed in clinical trials with atezolizumab (see section 4.8). Patients should be 
monitored for changes in renal function.  
 
Treatment with atezolizumab should be withheld for Grade 2 nephritis, and treatment with systemic 
corticosteroids at a dose of 1 to 2mg/kg/day of prednisone or equivalent should be started. Treatment 
with atezolizumab may be resumed if the event improves to ≤ Grade 1 within 12 weeks, and 
corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with 
atezolizumab must be permanently discontinued for Grade 3 or 4 nephritis. 
 
Immune-related myositis  
 
Cases of myositis, including fatal cases, have been observed in clinical trials with atezolizumab (see 
section 4.8). Patients should be monitored for signs and symptoms of myositis.  
 



48 
 
 

Treatment with atezolizumab should be withheld for Grade 2 or 3 myositis and corticosteroid therapy 
(1-2 mg/kg/day prednisone or equivalent) should be initiated. If symptoms improve to ≤ Grade 1, taper 
corticosteroids as clinically indicated. Treatment with atezolizumab may be resumed if the event 
improves to ≤ Grade 1 within 12 weeks, and corticosteroids have been reduced to ≤ 10 mg oral 
prednisone or equivalent per day. Treatment with atezolizumab should be permanently discontinued 
for Grade 4 or grade 3 recurrent myositis, or when unable to reduce the corticosteroid dose to the 
equivalent of ≤ 10 mg prednisone per day within 12 weeks after onset. 
 
Infusion-related reactions 
 
Infusion-related reactions have been observed with atezolizumab (see section 4.8).  
 
The rate of infusion should be reduced or treatment should be interrupted in patients with Grade 1 or 2 
infusion-related reactions. Atezolizumab should be permanently discontinued in patients with Grade 3 
or 4 infusion-related reactions. Patients with Grade 1 or 2 infusion-related reactions may continue to 
receive atezolizumab with close monitoring; premedication with antipyretic and antihistamines may be 
considered.  
 
Disease-specific precautions 
 
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin in metastatic 
non-squamous non-small cell lung cancer  
 
Physicians should carefully consider the combined risks of the four-drug regimen of atezolizumab 
bevacizumab, paclitaxel, and carboplatin before initiating treatment (see section 4.8). 
 
Use of atezolizumab in combination with nab-paclitaxel in metastatic triple negative breast cancer 
 
Neutropenia and peripheral neuropathies occurring during treatment with atezolizumab and nab-
paclitaxel may be reversible with interruptions of nab-paclitaxel. Physicians should consult the nab-
paclitaxel summary of product characteristics (SmPC) for specific precautions and contraindications 
of this medicine. 
 
Use of atezolizumab in urothelial carcinoma for previously untreated patients who are considered 
cisplatin ineligible 
 
The baseline and prognostic disease characteristics of the IMvigor210 Cohort 1 study population were 
overall comparable to patients in the clinic who would be considered cisplatin ineligible but would be 
eligible for a carboplatin-based combination chemotherapy. There are insufficient data for the 
subgroup of patients that would be unfit for any chemotherapy; therefore atezolizumab should be used 
with caution in these patients, after careful consideration of the potential balance of risks and benefits 
on an individual basis. 
 
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin  
 
Patients with NSCLC that had clear tumour infiltration into the thoracic great vessels or clear 
cavitation of pulmonary lesions, as seen on imaging, were excluded from the pivotal clinical study 
IMpower150 after several cases of fatal pulmonary haemorrhage were observed, which is a known 
risk factor of treatment with bevacizumab.  
 
In the absence of data, atezolizumab should be used with caution in these populations after careful 
evaluation of the balance of benefits and risks for the patient. 
 



49 
 
 

Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin in EGFR+ patients 
with NSCLC who have progressed on erlotinib+bevacizumab 
 
In study IMpower150, there are no data on the efficacy of atezolizumab in combination with 
bevacizumab, paclitaxel and carboplatin in EGFR+ patients who have progressed previously on 
erlotinib+bevacizumab.  
 
Use of atezolizumab in combination with bevacizumab in hepatocellular carcinoma 
 
Data in HCC patients with Child-Pugh B liver disease treated with atezolizumab in combination with 
bevacizumab are very limited and there are currently no data available in HCC patients with Child-
Pugh C liver disease.  
 
Patients treated with bevacizumab have an increased risk of haemorrhage, and cases of severe 
gastrointestinal haemorrhage, including fatal events, were reported in patients with hepatocellular 
carcinoma (HCC) treated with atezolizumab in combination with bevacizumab. In patients with HCC, 
screening for and subsequent treatment of oesophageal varices should be performed as per clinical 
practice prior to starting treatment with the combination of atezolizumab and bevacizumab. 
Bevacizumab should be permanently discontinued in patients who experience Grade 3 or 4 bleeding 
with the combination treatment. Please refer to the bevacizumab Summary of Product Characteristics. 
 
Diabetes mellitus can occur during treatment with atezolizumab in combination with bevacizumab. 
Physicians should monitor blood glucose levels prior to and periodically during treatment with 
atezolizumab in combination with bevacizumab as clinically indicated. 
 
Patients excluded from clinical trials 
 
Patients with the following conditions were excluded from clinical trials: a history of autoimmune 
disease, history of pneumonitis, active brain metastasis, HIV, hepatitis B or hepatitis C infection, 
significant cardiovascular disease and patients with inadequate hematologic and end-organ function.  
Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment; systemic 
immunostimulatory agents within 4 weeks or systemic immunosuppressive medicinal products within 
2 weeks prior to study entry; therapeutic oral or IV antibiotics within 2 weeks prior to initiation of 
study treatment were excluded from clinical trials.  
 
Patient card 
 
All prescribers of Tecentriq must be familiar with the Physician Information and Management 
Guidelines. The prescriber must discuss the risks of Tecentriq therapy with the patient. The patient 
will be provided with the patient card and instructed to carry the card at all times. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No formal pharmacokinetic drug interaction studies have been conducted with atezolizumab. Since 
atezolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions 
are expected.  
 
The use of systemic corticosteroids or immunosuppressants before starting atezolizumab should be 
avoided because of their potential interference with the pharmacodynamic activity and efficacy of 
atezolizumab. However, systemic corticosteroids or other immunosuppressants can be used to treat 
immune-related adverse reactions after starting atezolizumab (see section 4.4). 
 



50 
 
 

4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential have to use effective contraception during and for 5 months after 
treatment with atezolizumab. 
 
Pregnancy 
 
There are no data from the use of atezolizumab in pregnant women. No developmental and 
reproductive studies were conducted with atezolizumab. Animal studies have demonstrated that 
inhibition of the PD-L1/PD-1 pathway in murine pregnancy models can lead to immune-related 
rejection of the developing foetus resulting in foetal death (see section 5.3). These results indicate a 
potential risk, based on its mechanism of action, that administration of atezolizumab during pregnancy 
could cause foetal harm, including increased rates of abortion or stillbirth.  
 
Human immunoglobulins G1 (IgG1) are known to cross the placental barrier and atezolizumab is an 
IgG1; therefore, atezolizumab has the potential to be transmitted from the mother to the developing 
foetus.  
 
Atezolizumab should not be used during pregnancy unless the clinical condition of the woman 
requires treatment with atezolizumab. 
 
Breast-feeding 
 
It is unknown whether atezolizumab is excreted in human milk. Atezolizumab is a monoclonal 
antibody and is expected to be present in the first milk and at low levels afterwards. A risk to the 
newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding 
or to discontinue Tecentriq therapy taking into account the benefit of breast-feeding for the child and 
the benefit of therapy for the woman. 
 
Fertility 
 
No clinical data are available on the possible effects of atezolizumab on fertility. No reproductive and 
development toxicity studies have been conducted with atezolizumab; however, based on the 26-week 
repeat dose toxicity study, atezolizumab had an effect on menstrual cycles at an estimated AUC 
approximately 6 times the AUC in patients receiving the recommended dose and was reversible (see 
section 5.3). There were no effects on the male reproductive organs. 
 
4.7 Effects on ability to drive and use machines 
 
Tecentriq has minor influence on the ability to drive and use machines. Patients experiencing fatigue 
should be advised not to drive and use machines until symptoms abate (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of atezolizumab as monotherapy is based on pooled data in 3,568 patients across multiple 
tumour types. The most common adverse reactions (> 10%) were fatigue (34.5%), decreased appetite 
(24.0%), nausea (22.4%), pyrexia (20.1%), diarrhoea (19.9%), cough (19.8%), rash (19.8%), dyspnoea 
(19.0%), musculoskeletal pain (14.7%), back pain (14.4%), vomiting (14.1%), pruritus (14.0%), 
asthenia (13.9%), arthralgia (13.6%),  urinary tract infection (13.1%) and headache (10.9%). 
 



51 
 
 

The safety of atezolizumab given in combination with other medicinal products, has been evaluated in 
4,371 patients across multiple tumour types. The most common adverse reactions (≥ 20%) were 
anaemia (36.8 %), neutropenia (35.8 %), nausea (34.4 %), fatigue (33.0 %), thrombocytopenia 
(27.7 %), rash (27.2%), diarrhoea (27.1 %), alopecia (26.4%), constipation (25.7 %), decreased 
appetite (25.0%) and peripheral neuropathy (23.0 %). 
 
Further details on serious adverse reactions are provided in Section 4.4 Warnings & Precautions. 
  
Tabulated list of adverse reactions  
 
The Adverse Drug Reactions (ADRs) are listed by MedDRA system organ class (SOC) and categories 
of frequency in Table 2 for atezolizumab given as monotherapy or as combination therapy. Adverse 
reactions known to occur with atezolizumab or chemotherapies given alone may occur during 
treatment with these medicinal products in combination, even if these reactions were not reported in 
clinical trials with combination therapy. The following categories of frequency have been used: very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000), very rare (< 1/10,000). Within each frequency grouping, adverse reactions are presented in 
the order of decreasing seriousness. 
 
Table 2: Summary of adverse reactions occurring in patients treated with atezolizumab 
 

Atezolizumab monotherapy Atezolizumab in combination therapy 
Infections and infestations 
Very common urinary tract infectiona lung infectionb 

Common  sepsisaj 

Blood and lymphatic system disorders 
Very common  anaemia, thrombocytopeniad, neutropeniae, 

leukopeniaf 
Common thrombocytopeniad lymphopeniag 

Immune system disorders 
Common infusion-related reactionh infusion-related reactionh 

Endocrine disorders 
Very common  hypothyroidismi 
Common Hypothyroidismi hyperthyroidismj 

Uncommon hyperthyroidismj, diabetes 
mellitusk, adrenal insufficiencyl 

 

Rare hypophysitism  

Metabolism and nutrition disorders  
Very common decreased appetite decreased appetite  

Common hypokalaemiaae, hyponatraemiaaf, 
hyperglycaemia 

hypokalaemiaae, hyponatraemiaaf, 
hypomagnesaemian 

Nervous system disorders  
Very Common headache peripheral neuropathyo , headache 
Common  syncope, dizziness 
Uncommon Guillain-Barré syndromep, 

meningoencephalitisq 
 

Rare myasthenic syndromer  



52 
 
 

Atezolizumab monotherapy Atezolizumab in combination therapy 
Eye Disorders 

Rare uveitis  

Cardiac disorders 

Rare myocarditiss  

Vascular disorders 
Very Common  hypertensionai 

Common hypotension  

Respiratory, thoracic, and mediastinal disorders 
Very common cough, dyspnoea dyspnoea, cough 

Common pneumonitist, hypoxiaag, nasal 
congestion, nasopharyngitis 

dysphonia 

Gastrointestinal disorders 
Very common nausea, vomiting, diarrhoeau nausea, diarrhoeau, constipation, vomiting  

Common abdominal pain, colitisv, 
dysphagia, oropharyngeal painw 

stomatitis, dysgeusia 

Uncommon pancreatitisx  

Hepatobiliary disorders 
Common AST increased, ALT increased, 

hepatitisy 
AST increased, ALT increased 

Skin and subcutaneous tissue disorders 
Very Common rashz, pruritus rashz, pruritus, alopeciaah 

Common dry skin  

Uncommon psoriasis psoriasis 

Musculoskeletal and connective tissue disorders 
Very common arthralgia, back pain, 

musculoskeletal painaa 
arthralgia, musculoskeletal painaa, back pain 

Uncommon myositisab  

Renal and urinary disorders 
Common blood creatinine increasedc proteinuriaac, blood creatinine increasedc 

Rare nephritisad  

General disorders and administration site conditions 
Very Common pyrexia, fatigue, asthenia pyrexia, fatigue, asthenia, oedema peripheral 

Common influenza like illness, chills  

Investigations 

Common  blood alkaline phosphatase increased 
a Includes reports of urinary tract infection, cystitis, pyelonephritis, escherichia urinary tract infection, urinary 
tract infection bacterial, kidney infection, pyelonephritis acute, urinary tract infection fungal, urinary tract 
infection pseudomonal. 



53 
 
 

b Includes reports of pneumonia, bronchitis, lung infection, lower respiratory tract infection, infective 
exacerbation of COPD, infectious pleural effusion, tracheobronchitis, atypical pneumonia, lung abscess, 
paracancerous pneumonia, pyopneumothorax, pleural infection.  
c. Includes reports of blood creatinine increased, hypercreatininaemia 
d Includes reports of thrombocytopenia, platelet count decreased. 
e Includes reports of neutropenia, neutrophil count decreased, febrile neutropenia, neutropenic sepsis, 
granulocytopenia. 
f Includes reports of white blood cell count decreased, leukopenia. 
g. Includes reports of lymphopenia, lymphocyte count decreased 
h Includes reports of infusion related reaction, cytokine release syndrome, hypersensitivity, anaphylaxis. 
i Includes reports of autoimmune hypothyroidism, autoimmune thyroiditis, blood thyroid stimulating hormone 
abnormal, blood thyroid stimulating hormone decreased, blood thyroid stimulating hormone increased, euthyroid 
sick syndrome, goitre, hypothyroidism, myxedema coma, thyroid disorder, thyroid function test abnormal, 
thyroiditis, thyroxine decreased, thyroxine free decreased, thyroxine free increased, thyroxine increased, tri-
iodothyronine decreased, tri-iodothyronine free abnormal, tri-iodothyronine free decreased, tri-iodothyronine 
free increased, silent thyroiditis, thyroiditis chronic.  
j Includes reports of hyperthyroidism, Basedow’s disease, endocrine ophthalmopathy, exophthalmos. 
k Includes reports of diabetes mellitus, type 1 diabetes mellitus, diabetic ketoacidosis, ketoacidosis. 
l Includes reports of adrenal insufficiency, primary adrenal insufficiency. 
m Incudes reports of hypophysitis, temperature regulation disorder. 
n Includes reports of hypomagnesaemia, blood magnesium decreased 

o Includes reports of neuropathy peripheral, autoimmune neuropathy, peripheral sensory neuropathy, 
polyneuropathy, herpes zoster, peripheral motor neuropathy, neuralgic amyotrophy, peripheral sensorimotor 
neuropathy, toxic neuropathy, axonal neuropathy, lumbosacral plexopathy, neuropathic arthropathy, peripheral 
nerve infection. 
p Includes reports of Guillain-Barré syndrome, demyelinating polyneuropathy. 
q Includes reports of encephalitis, meningitis, photophobia. 
r Incudes reports of myasthenia gravis. 
s Reported in studies outside the pooled dataset. The frequency is based on the program wide exposure. 
t Includes reports of pneumonitis, lung infiltration, bronchiolitis, interstitial lung disease, radiation pneumonitis. 
u Includes reports of diarrhoea, defaecation urgency, frequent bowel movements, diarrhoea haemorrhagic. 
v Includes reports of colitis, autoimmune colitis, colitis ischaemic, colitis microscopic, colitis ulcerative. 
w Includes reports of oropharyngeal pain, oropharyngeal discomfort, throat irritation. 
x Includes reports of autoimmune pancreatitis, pancreatitis, pancreatitis acute, lipase increased, amylase 
increased. 
y Includes reports of ascites, autoimmune hepatitis, hepatocellular injury, hepatitis, hepatitis acute, 
hepatotoxicity, liver disorder, drug-induced liver injury, hepatic failure, hepatic steatosis, hepatic lesion, 
oesophageal varices haemorrhage, varices oesophageal. 
z Includes reports of acne, acne pustular, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis bullous, 
dermatitis exfoliative generalised, drug eruption, eczema, eczema infected, erythema, erythema multiforme, 
erythema of eyelid, exfoliative rash, folliculitis, furuncle, palmar-plantar erythrodysaesthesia syndrome, rash , 
rash erythematous, rash follicular, rash generalised, rash macular, rash maculo-papular, rash papular, rash 
pruritic, rash pustular, rash vesicular, seborrhoeic dermatitis, skin exfoliation, skin toxicity, skin ulcer, toxic 
epidermal necrolysis, toxic skin eruption. 
aa Includes reports of musculoskeletal pain, myalgia, bone pain. 
ab Includes reports of myositis, rhabdomyolysis, polymyalgia rheumatica, dermatomyositis, muscle abscess, 
myoglobin urine present. 
ac Includes reports of proteinuria, protein urine present, haemoglobinurea, urine abnormality,nephrotic syndrome, 
albuminuria. 
ad Includes report of nephritis, Henoch-Schonlein Purpura nephritis. 
ae Includes report of hypokalaemia, blood potassium decreased. 
af Includes report of hyponatraemia, blood sodium decreased. 
ag Includes report of hypoxia, oxygen saturation decreased. 
ah Includes report of alopecia, madarosis, alopecia areata, alopecia totalis, hypotrichosis. 
ai Includes reports of hypertension, blood pressure increased, hypertensive crisis, blood pressure systolic 
increased, diastolic hypertension, blood pressure inadequately controlled, retinopathy hypertensive, hypertensive 
nephropathy, essential hypertension. 
aj Includes  reports of sepsis, septic shock, urosepsis, neutropenic sepsis, pulmonary sepsis, bacterial sepsis, 
klebsiella sepsis, abdominal sepsis, candida sepsis, escherichia sepsis, pseudomonal sepsis, staphylococcal 
sepsis. 
 



54 
 
 

Description of selected adverse reactions 
 
The data below reflect information for significant adverse reactions for atezolizumab as monotherapy 
in clinical studies (see section 5.1). Details for the significant adverse reactions for atezolizumab when 
given in combination are presented if clinically relevant differences were noted in comparison to 
atezolizumab monotherapy. The management guidelines for these adverse reactions are described in 
sections 4.2 and 4.4. 
 
Immune-related pneumonitis 
 
Pneumonitis occurred in 2.8% (99/3,568) of patients who received atezolizumab monotherapy. Of the 
99 patients, one experienced a fatal event. The median time to onset was 4.0 months (range 3 days to 
24.8 months). The median duration was 1.6 months (range 0 day to 21.7+ months; + denotes a 
censored value). Pneumonitis led to discontinuation of atezolizumab in 15 (0.4%) patients. 
Pneumonitis requiring the use of corticosteroids occurred in 1.5% (53/3,568) of patients receiving 
atezolizumab monotherapy.  
 
Immune-related hepatitis  
 
Hepatitis occurred in 1.8% (66/3,568) of patients who received atezolizumab monotherapy. Of the 66 
patients, two experienced a fatal event. The median time to onset was 1.5 months (range 6 days to 18.8 
months). The median duration was 2.1 months (range 0 day to 22.0+ months; + denotes a censored 
value). Hepatitis led to discontinuation of atezolizumab in 9 ( 0.3%) patients. Hepatitis requiring the 
use of corticosteroids occurred in 0.5% (19/3,568) of patients receiving atezolizumab monotherapy.  
 
Immune-related colitis 
 
Colitis occurred in 1.2 % (43/3,568) of patients who received atezolizumab monotherapy. The median 
time to onset was 5.0 months (range 15 days to 17.2 months). The median duration was 1.2 months 
(range 3 days to 17.8+ months; + denotes a censored value). Colitis led to discontinuation of 
atezolizumab in 15 (0.4%) patients. Colitis requiring the use of corticosteroids occurred in 0.5% 
(19/3,568) of patients receiving atezolizumab monotherapy.  
 
Immune-related endocrinopathies  
 
Thyroid disorders  
 
Hypothyroidism occurred in 6.0% (214/3,568) of patients who received atezolizumab monotherapy. 
The median time to onset was 4.4 months (range: 0 day to 31.3 months). Hyperthyroidism occurred in 
1.3% (47/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 
2.1 months (range 21 days to 15.7 months).  
 
Adrenal insufficiency 
 
Adrenal insufficiency occurred in 0.4% (13/3,568) of patients who received atezolizumab 
monotherapy. The median time to onset was 5.7 months (range: 3 days to 19 months). The median 
duration was 16.8 months (range: 0 day to 20.9+ months; + denotes a censored value). Adrenal 
insufficiency led to discontinuation of atezolizumab in 1 (<0.1%) patient. Adrenal insufficiency 
requiring the use of corticosteroids occurred in 0.3% (10/3,568) of patients receiving atezolizumab 
monotherapy. 
 
Hypophysitis 
 
Hypophysitis occurred in < 0.1% (3/3,568) of patients who received atezolizumab monotherapy. The 
median time to onset 5.3 months (range: 24 days to 13.7 months). Two (<0.1%) patients required the 
use of corticosteroids and treatment with atezolizumab was discontinued in 1 (<0.1%) patient. 



55 
 
 

 
Hypophysitis occurred in 0.8% (3/393) of patients who received atezolizumab with bevacizumab, 
paclitaxel, and carboplatin. The median time to onset was 7.7 months (range: 5.0 to 8.8 months). Two 
patients required the use of corticosteroids. 
 
Hypophysitis occurred in 0.4% (2/473) of patients who received atezolizumab in combination with 
nab-paclitaxel and carboplatin. The median time to onset was 5.2 months (range: 5.1 to 5.3 months). 
Both patients required the use of corticosteroids.  
 
Diabetes mellitus  
 
Diabetes mellitus occurred in 0.3% (11/3,568) of patients who received atezolizumab monotherapy. 
The median time to onset was 4.2 months (range 3 days to 9.9 months). Diabetes mellitus led to the 
discontinuation of atezolizumab in < 0.1% (3/3,568) patients. 
 
Diabetes mellitus occurred in 2.0% (10/493) of HCC patients who received atezolizumab in 
combination with bevacizumab. The median time to onset was 4.4 months (range: 1.2 months - 8.3 
months). No events of diabetes mellitus led to atezolizumab withdrawal.   
 
Immune-related meningoencephalitis  
 
Meningoencephalitis occurred in 0.4% (14/3,568) of patients who received atezolizumab 
monotherapy. The median time to onset was 15 days (range: 0 day to 12.5 months). The median 
duration was 21 days (range 6 days to 14.5+ months; + denotes a censored value).  
 
Meningoencephalitis requiring the use of corticosteroids occurred in 0.2% (6/3,568) of patients 
receiving atezolizumab and four patients discontinued atezolizumab.  
 
Immune-related neuropathies 
 
Guillain-Barré syndrome and demyelinating polyneuropathy occurred in 0.1% (5/3,568) of patients 
who received atezolizumab monotherapy. The median time to onset was 7 months (range: 18 days to 
8.1 months). The median duration was 8.0 months (range 18 days to 8.3+ months; + denotes a 
censored value). Guillain-Barré syndrome led to discontinuation of atezolizumab in 1 patient (< 0.1%). 
Guillain-Barré syndrome requiring the use of corticosteroids occurred in < 0.1% (2/3,568) of patients 
receiving atezolizumab monotherapy. 
 
Myasthenic syndrome  
 
Myasthenia gravis occurred in < 0.1% (1/3,568) of patients who received atezolizumab monotherapy. 
The time to onset was 1.2 months.  
 
Immune-related pancreatitis 
 
Pancreatitis, including amylase increased and lipase increased, occurred in 0.8% (27/3,568) of patients 
who received atezolizumab monotherapy. The median time to onset was 4.3 months (range: 0 days to 
16.9 months). The median duration was 27 days (range 3 days to 22.4+ months; + denotes a censored 
value). Pancreatitis led to the discontinuation of atezolizumab in 3 (< 0.1%) patients. Pancreatitis 
requiring the use of corticosteroids occurred in 0.1% (4/3,568) of patients receiving atezolizumab 
monotherapy. 
 



56 
 
 

Immune-related myocarditis  
 
Myocarditis occurred in < 0.1% (2/8,000) of patients across all atezolizumab clinical trials in multiple 
tumour types and treatment combinations. The time to onset was 18 and 33 days. Both patients 
required corticosteroids and discontinued atezolizumab.  
 
Immune-related nephritis 
 
Nephritis occurred in 0.2% (8/3,568) of patients who received atezolizumab. The median time to onset 
was 6.0 months (range: 2.0 to 17.5 months). Nephritis led to discontinuation of atezolizumab in 
4/3,568 (0.1%) patients. Two (<0.1%) patients required corticosteroids. 
 
Immune-related myositis 
 
Myositis occurred in 0.4% (15/3,568) of patients who received atezolizumab monotherapy. The 
median time to onset was 2.9 months (range: 0.4 to 11.0 months). The median duration was 3.8 
months (range 3 days to 22.6+ months; + denotes a censored value). Myositis led to discontinuation of 
atezolizumab in 1 (<0.1%) patient. Seven (0.2%) patients required the use of corticosteroids.  
 
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin  
 
In the first-line NSCLC study (IMpower150), an overall higher frequency of adverse events was 
observed in the four-drug regimen of atezolizumab, bevacizumab, paclitaxel, and carboplatin 
compared to atezolizumab, paclitaxel and carboplatin, including Grade 3 and 4 events (63.6% 
compared to 57.5%), Grade 5 events (6.1% compared to 2.5%), adverse events of special interest to 
atezolizumab (52.4% compared to 48.0%), as well as adverse events leading to withdrawal of any 
study treatment (33.8% compared to 13.3%). Nausea, diarrhoea, stomatitis, fatigue, pyrexia, mucosal 
inflammation, decreased appetite, weight decreased, hypertension and proteinuria were reported 
higher (≥5% difference) in patients receiving atezolizumab in combination with bevacizumab, 
paclitaxel and carboplatin. Other clinically significant adverse events which were observed more 
frequently in the atezolizumab, bevacizumab, paclitaxel, and carboplatin arm were epistaxis, 
haemoptysis, cerebrovascular accident, including fatal events. 
 
Immunogenicity 
 
Across multiple phase III studies, 13.1 % to 36.4% of patients developed treatment-emergent anti-drug 
antibodies (ADAs).  
 
Across pooled datasets for patients treated with atezolizumab monotherapy (N=2705) and with 
combination therapies (N= 2285), the following rates of adverse events (AEs) have been observed for 
the ADA-positive population compared to the ADA-negative population, respectively: Grade 3-4 AEs 
49.1% vs. 44.3%,  Serious Adverse Events (SAEs) 42.4% vs. 37.6%, AEs leading to treatment 
withdrawal 6.1% vs 6.7% (for monotherapy); Grade 3-4 AEs 63.9% vs. 60.9%, SAEs 43.9% vs. 
35.6%, AEs leading to treatment withdrawal 22.8% vs 18.4% (for combination therapy). However, 
available data do not allow firm conclusions to be drawn on possible patterns of adverse drug 
reactions.  
 
Paediatric population 
 
The safety of atezolizumab in children and adolescents has not been established. No new safety signals 
were observed in a clinical study with 69 paediatric patients (<18 years) and the safety profile was 
comparable to adults. 
 



57 
 
 

Elderly patients 
 
No overall differences in safety were observed between patients ≥ 65 years of age and younger 
patients receiving atezolizumab monotherapy. In study IMpower150, age ≥ 65 was associated with an 
increased risk of developing adverse events in patients receiving atezolizumab in combination with 
bevacizumab, carboplatin and paclitaxel. 
 
In studies IMpower150 and IMpower133, data for patients ≥75 years of age are too limited to draw 
conclusions on this population.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
There is no information on overdose with atezolizumab.  
 
In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, 
and appropriate symptomatic treatment instituted. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies. ATC code: L01XC32 
 
Mechanism of action 
 
Programmed death-ligand 1 (PD-L1) may be expressed on tumour cells and/or tumour-infiltrating 
immune cells, and can contribute to the inhibition of the antitumour immune response in the tumour 
microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T-cells and antigen 
presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production.  
 
Atezolizumab is an Fc-engineered, humanised immunoglobulin G1 (IgG1) monoclonal antibody that 
directly binds to PD-L1 and provides a dual blockade of the PD-1 and B7.1 receptors, releasing 
PD-L1/PD-1 mediated inhibition of the immune response, including reactivating the antitumour 
immune response without inducing antibody-dependent cellular cytotoxicity. Atezolizumab spares the 
PD-L2/PD-1 interaction allowing PD-L2/PD-1 mediated inhibitory signals to persist.  
 
Clinical efficacy and safety 
 
Duration of treatment 
 
Treatment with atezolizumab until loss of clinical benefit was permitted as defined by the following 
criteria: 
• Absence of symptoms and signs (including worsening of laboratory values [e.g., new or 

worsening hypercalcaemia]) indicating unequivocal progression of disease 
• No decline in ECOG performance status  
• Absence of tumour progression at critical anatomical sites (e.g., leptomeningeal disease) that 

cannot be readily managed and stabilised by protocol-allowed medical interventions prior to 
repeat dosing 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


58 
 
 

• Evidence of clinical benefit as assessed by the investigator 
 
Patients with ES-SCLC were treated with atezolizumab until disease progression. Treatment beyond 
disease progression was permitted at the discretion of the physician. 
 
Patients with locally advanced or metastatic UC who are ineligible for cisplatin therapy were treated 
with atezolizumab until disease progression. 
 
Urothelial carcinoma 
 
IMvigor211 (GO29294): Randomised trial in locally advanced or metastatic UC patients previously 
treated with chemotherapy 
 
A phase III, open-label, multi-center, international, randomised study, (IMvigor211), was conducted to 
evaluate the efficacy and safety of atezolizumab compared with chemotherapy (investigator’s choice 
of vinflunine, docetaxel, or paclitaxel) in patients with locally advanced or metastatic UC who 
progressed during or following a platinum-containing regimen. This study excluded patients who had 
a history of autoimmune disease; active or corticosteroid-dependent brain metastases; administration 
of a live, attenuated vaccine within 28 days prior to enrolment; and administration of systemic 
immunostimulatory agents within 4 weeks or systemic immunosuppressive medicinal product within 
2 weeks prior to enrolment. Tumour assessments were conducted every 9 weeks for the first 54 weeks, 
and every 12 weeks thereafter. Tumour specimens were evaluated prospectively for PD-L1 expression 
on tumour-infiltrating immune cells (IC) and the results were used to define the PD-L1 expression 
subgroups for the analyses described below.  
 
A total of 931 patients were enrolled. Patients were randomised (1:1) to receive either atezolizumab or 
chemotherapy. Randomisation was stratified by chemotherapy (vinflunine vs. taxane), PD-L1 
expression status on IC (< 5% vs. ≥ 5%), number of prognostic risk factors (0 vs. 1-3), and liver 
metastases (yes vs. no). Prognostic risk factors included time from prior chemotherapy of < 3 months, 
ECOG performance status > 0 and haemoglobin < 10 g/dL. 
 
Atezolizumab was administered as a fixed dose of 1,200 mg by intravenous infusion every 3 weeks. 
No dose reduction of atezolizumab was allowed. Patients were treated until loss of clinical benefit as 
assessed by the investigator or unacceptable toxicity. Vinflunine was administered 320 mg/m2 by 
intravenous infusion on day 1 of each 3-week cycle until disease progression or unacceptable toxicity. 
Paclitaxel was administered 175 mg/m2 by intravenous infusion over 3 hours on day 1 of each 3-week 
cycle until disease progression or unacceptable toxicity. Docetaxel was administered 75 mg/m2 by 
intravenous infusion on day 1 of each 3-week cycle until disease progression or unacceptable toxicity. 
For all treated patients, the median duration of treatment was 2.8 months for the atezolizumab arm, 
2.1 months for the vinflunine and paclitaxel arms and 1.6 months for the docetaxel arm. 
 
The demographic and baseline disease characteristics of the primary analysis population were well 
balanced between the treatment arms. The median age was 67 years (range: 31 to 88), and 77.1% of 
patients were male. The majority of patients were white (72.1%), 53.9% of patients within the 
chemotherapy arm received vinflunine, 71.4% of patients had at least one poor prognostic risk factor 
and 28.8% had liver metastases at baseline. Baseline ECOG performance status was 0 (45.6%) or 1 
(54.4%). Bladder was the primary tumour site for 71.1% of patients and 25.4% of patients had upper 
tract urothelial carcinoma. There were 24.2% of patients who received only prior platinum-containing 
adjuvant or neoadjuvant therapy and progressed within 12 months. 
 
The primary efficacy endpoint for IMvigor211 is overall survival (OS). Secondary efficacy endpoints 
evaluated per investigator-assessed Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 are 
objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR). 
Comparisons with respect to OS between the treatment arm and control arm within the IC2/3, IC1/2/3, 
and ITT (Intention-to-treat, i.e. all comers) populations were tested using a hierarchical fixed-sequence 
procedure based on a stratified log-rank test at two-sided level of 5% as follows: step 1) IC2/3 



59 
 
 

population; step 2) IC1/2/3 population; step 3) all comers population. OS results for each of steps 2 
and 3 could be formally tested for statistical significance only if the result in the preceding step was 
statistically significant. 
 
The median survival follow-up is 17 months. The primary analysis of study IMvigor211 did not meet 
its primary endpoint of OS. Atezolizumab did not demonstrate a statistically significant survival 
benefit compared to chemotherapy in patients with previously treated, locally advanced or metastatic 
urothelial carcinoma. Per the pre-specified hierarchical testing order, the IC2/3 population was tested 
first, with an OS HR of 0.87 (95% CI: 0.63, 1.21; median OS of 11.1 vs. 10.6 months for atezolizumab 
and chemotherapy respectively). The stratified log-rank p-value was 0.41 and therefore the results are 
considered not statistically significant in this population. As a consequence, no formal tests of 
statistical significance could be performed for OS in the IC1/2/3 or all comer populations, and results 
of those analyses would be considered exploratory. The key results in the all comer population are 
summarised in Table 3. The Kaplan-Meier curve for OS in the all comer population is presented in 
Figure 1. 
 
An exploratory updated survival analysis was performed with a median duration of survival follow up 
of 34 months in the ITT population. The median OS was 8.6 months (95% CI: 7.8, 9.6) in the 
atezolizumab arm and 8.0 months (95% CI: 7.2, 8.6) in the chemotherapy arm with a hazard ratio of 
0.82 (95% CI: 0.71, 0.94). Consistent with the trend observed at primary analysis for 12-month OS 
rates, numerically higher 24-month and 30-month OS rates were observed for patients in the 
atezolizumab arm compared with the chemotherapy arm in the ITT population. The percentage of 
patients alive at 24 months (KM estimate) was 12.7% in the chemotherapy arm and 22.5% in the 
atezolizumab arm; and at 30 months (KM estimate) was 9.8% in the chemotherapy arm and 18.1% in 
the atezolizumab arm. 
 



60 
 
 

Table 3: Summary of efficacy in all comers (IMvigor211) 
 

Efficacy endpoint 
Atezolizumab 

(n = 467) 
Chemotherapy 

(n = 464) 
Primary efficacy endpoint 
OS* 
   No. of deaths (%) 324 (69.4%) 350 (75.4%) 
   Median time to events (months)  8.6 8.0 
   95% CI 7.8, 9.6 7.2, 8.6 

   Stratifiedǂ hazard ratio (95% CI) 0.85 (0.73, 0.99) 

12-month OS (%)** 39.2% 32.4% 
Secondary and exploratory endpoints 
Investigator-assessed PFS (RECIST v1.1) 
   No. of events (%) 407 (87.2%) 410 (88.4%) 
   Median duration of PFS (months) 2.1 4.0 
   95% CI 2.1, 2.2 3.4, 4.2 
   Stratified hazard ratio (95% CI) 1.10 (0.95, 1.26) 
Investigator-assessed ORR (RECIST v1.1) n = 462 n = 461 
   No. of confirmed responders (%) 62 (13.4%) 62 (13.4%) 
   95% CI 10.45, 16.87 10.47, 16.91 
No. of complete response (%) 16 (3.5%) 16 (3.5%) 
No. of partial response (%) 46 (10.0%) 46 (10.0%) 
No. of stable disease (%) 92 (19.9%) 162 (35.1%) 
Investigator-assessed DOR (RECIST v1.1) n = 62 n = 62 
   Median in months *** 21.7 7.4 
   95% CI 13.0, 21.7 6.1, 10.3 

CI = confidence interval; DOR = duration of response; ORR = objective response rate; OS = overall survival; 
PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumours v1.1. 
* An analysis of OS in the all comer population was performed based on the stratified log-rank test and the result 
is provided for descriptive purposes only (p = 0.0378); according to the pre-specified analysis hierarchy, the 
p-value for the OS analysis in the all comer population cannot be considered statistically significant. 
ǂ Stratified by chemotherapy (vinflunine vs. taxane), status on IC (< 5% vs. ≥ 5%), number of prognostic risk 
factors (0 vs. 1-3), and liver metastases (yes vs. no). 
** Based on Kaplan-Meier estimate 
*** Responses were ongoing in 63% of responders in the atezolizumab arm and in 21% of responders in the 
chemotherapy arm. 
 



61 
 
 

Figure 1: Kaplan-Meier curve for overall survival (IMvigor211) 
 

 
 
IMvigor210 (GO29293): Single-arm trial in previously untreated urothelial carcinoma patients who 
are ineligible for cisplatin therapy and in urothelial carcinoma patients previously treated with 
chemotherapy 
 
A phase II, multi-centre, international, two-cohort, single-arm clinical trial, IMvigor210, was 
conducted in patients with locally advanced or metastatic UC (also known as urothelial bladder 
cancer).  
 
The study enrolled a total of 438 patients and had two patient cohorts. Cohort 1 included previously 
untreated patients with locally advanced or metastatic UC who were ineligible or unfit for 
cisplatin-based chemotherapy or had disease progression at least 12 months after treatment with a 
platinum-containing neoadjuvant or adjuvant chemotherapy regimen. Cohort 2 included patients who 
received at least one platinum-based chemotherapy regimen for locally advanced or metastatic UC or 
had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or 
adjuvant chemotherapy regimen. 
 
In Cohort 1, 119 patients were treated with atezolizumab 1,200 mg by intravenous infusion every 
3 weeks until disease progression. The median age was 73 years. Most patients were male (81%), and 
the majority of patients were White (91%).  
 
Cohort 1 included 45 patients (38%) with ECOG performance status of 0, 50 patients (42%) with 
ECOG performance status of 1 and 24 patients (20%) with ECOG performance status of 2, 35 patients 
(29%) with no Bajorin risk factors (ECOG performance status ≥ 2 and visceral metastasis), 66 patients 
(56%) with one Bajorin risk factor and 18 patients (15 %) with two Bajorin risk factors, 84 patients 
(71%) with impaired renal function (glomerular filtration rate [GFR] < 60 mL/min), and 25 patients 
(21%) with liver metastasis. 
 
The primary efficacy endpoint for Cohort 1 was confirmed objective response rate (ORR) as assessed 
by an independent review facility (IRF) using RECIST v1.1.  
 
The primary analysis was performed when all patients had at least 24 weeks of follow-up. Median 
duration of treatment was 15.0 weeks and median duration of survival follow-up was 8.5 months in all 
comers. Clinically relevant IRF-assessed ORRs per RECIST v1.1 were shown; however, when 
compared to a pre-specified historical control response rate of 10%, statistical significance was not 



62 
 
 

reached for the primary endpoint. The confirmed ORRs per IRF-RECIST v1.1 were 21.9% (95% CI: 
9.3, 40.0) in patients with PD-L1 expression ≥ 5%, 18.8% (95% CI: 10.9, 29.0) in patients with PD-L1 
expression ≥ 1%, and 19.3% (95% CI: 12.7, 27.6) in all comers. The median duration of response 
(DOR) was not reached in any PD-L1 expression subgroup or in all comers. OS was not mature with 
an event patient ratio of approximately 40%. Median OS for all patient subgroups (PD-L1 expression 
≥ 5 % and ≥ 1 %) and in all comers was 10.6 months.  
 
An updated analysis was performed with a median duration of survival follow-up of 17.2 months for 
Cohort 1 and is summarised in Table 4. The median DOR was not reached in any PD-L1 expression 
subgroup or in all comers. 
 
Table 4: Summary of updated efficacy (IMvigor210 Cohort 1) 
 

Efficacy endpoint 
PD-L1 

expression of  
≥ 5% in IC 

PD-L1 
expression of  
≥ 1% in IC 

All Comers 

ORR (IRF-assessed; RECIST v1.1) n = 32 n = 80 n = 119 

No. of Responders (%) 9 (28.1%) 19 (23.8%) 27 (22.7%) 
95% CI 13.8, 46.8 15.0, 34.6 15.5, 31.3 

No. of complete response (%) 
95% CI 

4 (12.5%) 
(3.5, 29.0) 

8 (10.0%) 
(4.4, 18.8) 

11 (9.2%) 
(4.7, 15.9) 

No. of partial response (%) 
95% CI 

5 (15.6%) 
(5.3, 32.8) 

11 (13.8%) 
(7.1, 23.3) 

16 (13.4%) 
(7.9, 20.9) 

DOR (IRF-assessed; RECIST v1.1) n = 9 n = 19 n = 27 

Patients with event (%) 3 (33.3%) 5 (26.3%) 8 (29.6%) 
Median (months) (95% CI) NE (11.1, NE) NE (NE) NE (14.1, NE) 

PFS (IRF-assessed; RECIST v1.1) n = 32 n = 80 n = 119 

Patients with event (%) 24 (75.0%) 59 (73.8%) 88 (73.9%) 
Median (months) (95% CI) 4.1 (2.3, 11.8) 2.9 (2.1, 5.4) 2.7 (2.1, 4.2) 

OS n = 32 n = 80 n = 119 

Patients with event (%) 18 (56.3%) 42 (52.5%) 59 (49.6%) 
Median (months) (95% CI) 12.3 (6.0, NE) 14.1 (9.2, NE) 15.9 (10.4, NE) 
1-year OS rate (%) 52.4% 54.8% 57.2% 

CI = confidence interval; DOR=duration of response; IC = tumour-infiltrating immune cells; IRF = independent 
review facility; NE = not estimable; ORR = objective response rate; OS = overall survival; 
PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumours v1.1. 
 
In Cohort 2, the co-primary efficacy endpoints were confirmed ORR as assessed by an IRF using 
RECIST v1.1 and investigator-assessed ORR according to Modified RECIST (mRECIST) criteria. 
There were 310 patients treated with atezolizumab 1,200 mg by intravenous infusion every 3 weeks 
until loss of clinical benefit. The primary analysis of Cohort 2 was performed when all patients had at 
least 24 weeks of follow-up. The study met its co-primary endpoints in Cohort 2, demonstrating 
statistically significant ORRs per IRF-assessed RECIST v1.1 and investigator-assessed mRECIST 
compared to a pre-specified historical control response rate of 10%. 
 
An analysis was also performed with a median duration of survival follow-up of 21.1 months for 
Cohort 2. The confirmed ORRs per IRF-RECIST v1.1 were 28.0% (95% CI: 19.5, 37.9) in patients 
with PD-L1 expression ≥ 5%, 19.3% (95% CI: 14.2, 25.4) in patients with PD-L1 expression ≥ 1%, 
and 15.8% (95% CI: 11.9, 20.4) in all comers. The confirmed ORR per investigator-assessed 
mRECIST was 29.0% (95% CI: 20.4, 38.9) in patients with PD-L1 expression ≥ 5%, 23.7% (95% CI: 
18.1, 30.1) in patients with PD-L1 expression ≥ 1%, and 19.7% (95% CI: 15.4, 24.6) in all comers. 



63 
 
 

The rate of complete response per IRF-RECIST v1.1 in the all comer population was 6.1% (95% CI: 
3.7, 9.4). For Cohort 2, median DOR was not reached in any PD-L1 expression subgroup or in all 
comers, however was reached in patients with PD-L1 expression < 1% (13.3 months; 95% CI 4.2, 
NE). The OS rate at 12 month was 37% in all comers.  
 
IMvigor130 (WO30070): Phase III multi-center, randomised, placebo-controlled study of 
atezolizumab as monotherapy and in combination with platinum-based chemotherapy in patients with 
untreated locally advanced or metastatic urothelial carcinoma 
 
Based on an independent Data Monitoring Committee (iDMC) recommendation following an early 
review of survival data, accrual of patients on the atezolizumab monotherapy treatment arm whose 
tumours have a low PD-L1 expression (less than 5% of immune cells staining positive for PD-L1 by 
immunohistochemistry) was stopped after observing decreased overall survival for this subgroup. The 
iDMC did not recommend any change of therapy for patients who had already been randomised to and 
were receiving treatment in the monotherapy arm. No other changes were recommended. 
 
Non-small cell lung cancer  
 
First-line treatment of non-small cell lung cancer 
 
IMpower150 (GO29436): Randomised phase III trial in chemotherapy-naïve patients with metastatic 
non-squamous NSCLC, in combination with paclitaxel and carboplatin with or without bevacizumab 
 
A phase III, open-label, multicenter, international, randomised study, IMpower150, was conducted to 
evaluate the efficacy and safety of atezolizumab in combination with paclitaxel and carboplatin, with 
or without bevacizumab, in chemotherapy-naïve patients with metastatic non-squamous NSCLC.  
 
Patients were excluded if they had history of autoimmune disease, administration of a live, attenuated 
vaccine within 28 days prior to randomisation, administration of systemic immunostimulatory agents 
within 4 weeks or systemic immunosuppressive medicinal product within 2 weeks prior to 
randomisation, active or untreated CNS metastases, clear tumour infiltration into the thoracic great 
vessels or clear cavitation of pulmonary lesions, as seen on imaging. Tumour assessments were 
conducted every 6 weeks for the first 48 weeks following Cycle 1, Day 1 and then every 9 weeks 
thereafter. Tumour specimens were evaluated for PD-L1 expression on tumour cells (TC) and 
tumour-infiltrating immune cells (IC) and the results were used to define the PD-L1 expression 
subgroups for the analyses described below.  
 
A total of 1,202 patients were enrolled and were randomised (1:1:1) to receive one of the treatment 
regimens described in Table 5. Randomisation was stratified by sex, presence of liver metastases and 
PD-L1 tumour expression on TC and IC. 
 



64 
 
 

Table 5: Intravenous treatment regimens (IMpower150)  
 

Treatment 
regimen 

Induction 
(Four or Six 21-day cycles) 

Maintenance 
(21-day cycles) 

A Atezolizumaba (1,200 mg) + paclitaxel 
(200 mg/m2)b,c + carboplatinc (AUC 6) 

Atezolizumaba (1,200 mg) 

B Atezolizumaba (1,200 mg) + bevacizumabd 
(15 mg/kg) + paclitaxel (200 mg/m2)b,c + 

carboplatinc (AUC 6) 

Atezolizumaba (1,200 mg) 
+ bevacizumabd (15 mg/kg) 

C Bevacizumabd (15 mg/kg) + paclitaxel 
(200 mg/m2)b,c + carboplatinc (AUC 6) 

Bevacizumabd (15 mg/kg) 

a Atezolizumab is administered until loss of clinical benefit as assessed by the investigator 
b The paclitaxel starting dose for patients of Asian race/ethnicity was 175 mg/m2 due to higher overall level of 
haematologic toxicities in patients from Asian countries compared with those from non-Asian countries 
c Paclitaxel and carboplatin are administered until completion of 4 or 6 cycles, or progressive disease, or 
unacceptable toxicity whichever occurs first 
d. Bevacizumab is administered until progressive disease or unacceptable toxicity 
 
The demographics and baseline disease characteristics of the study population were well balanced 
between the treatment arms. The median age was 63 years (range: 31 to 90), and 60% of patients were 
male. The majority of patients were white (82%). Approximately 10% of patients had known EGFR 
mutation, 4% had known ALK rearrangements, 14% had liver metastasis at baseline, and most 
patients were current or previous smokers (80%). Baseline ECOG performance status was 0 (43%) or 
1 (57%). 51% of patients’ tumours had PD-L1 expression of ≥ 1% TC or ≥ 1% IC and 49% of 
patients’ tumours had PD-L1 expression of < 1% TC and < 1% IC. 
 
At the time of the final analysis for PFS, patients had a median follow up time of 15.3 months. The 
ITT population, including patients with EGFR mutations or ALK rearrangements who should have 
been previously treated with tyrosine kinase inhibitors, demonstrated clinically meaningful PFS 
improvement in Arm B as compared to Arm C (HR of 0.61, 95% CI: 0.52, 0.72; median PFS 8.3 vs. 
6.8 months).   
 
At the time of the interim OS analysis, patients had a median follow-up of 19.7 months. The key 
results from this analysis as well as from the updated PFS analysis in the ITT population are 
summarised in Tables 6 and 7. The Kaplan-Meier curve for OS in the ITT population is presented in 
Figure 2. Figure 3 summarises the results of OS in the ITT and PD-L1 subgroups. Updated PFS results 
are also presented in Figures 4 and 5.  
 



65 
 
 

Table 6: Summary of updated efficacy in the ITT population (IMpower150) 
 

Efficacy endpoint Arm A 
(Atezolizumab + 

Paclitaxel + 
Carboplatin)  

Arm B 
(Atezolizumab + 
Bevacizumab + 

Paclitaxel + 
Carboplatin) 

Arm C 
(Bevacizumab 
+ Paclitaxel + 
Carboplatin) 

Secondary Endpoints#    
Investigator-assessed PFS (RECIST 
v1.1)* 

n = 402 n = 400 n = 400 

No. of events (%) 330 (82.1%) 291 (72.8%) 355 (88.8%) 
Median duration of PFS (months) 6.7 8.4 6.8 
95% CI (5.7, 6.9) (8.0, 9.9) (6.0, 7.0) 
Stratified hazard ratio‡^ (95% CI) 
p-value1,2 

0.91 (0.78, 1.06) 
0.2194 

0.59 (0.50, 0.69) 
< 0.0001 

--- 

12-month PFS (%) 24 38 20 
OS interim analysis* n = 402  n = 400  n = 400 
No. of deaths (%) 
Median time to events (months) 
95% CI 

206 (51.2%) 
19.5  

(16.3, 21.3) 

192 (48.0%) 
19.8 

(17.4, 24.2) 

230 (57.5%) 
14.9 

(13.4, 17.1) 
Stratified hazard ratio‡^ (95% CI) 
p-value1,2 

0.85 (0.71, 1.03) 
0.0983 

0.76 (0.63, 0.93) 
0.006 

--- 

6-month OS (%) 84 85 81 
12-month OS (%) 66 68 61 
Investigator-assessed Overall Best 
Response3* (RECIST 1.1) 

n = 401 n = 397 n = 393 

No. of responders (%) 163 (40.6%) 224 (56.4%) 158 (40.2%) 
95% CI (35.8, 45.6) (51.4, 61.4) (35.3, 45.2) 
No. of complete response (%) 8 (2.0%) 11 (2.8%) 3 (0.8%) 
No. of partial response (%) 155 (38.7%) 213 (53.7%) 155 (39.4%) 
Investigator-assessed DOR* (RECIST 
v1.1) 

n = 163 n = 224 n = 158 

Median in months 8.3 11.5 6.0 
95% CI (7.1, 11.8) (8.9, 15.7) (5.5, 6.9) 
# Primary efficacy endpoints were PFS and OS and they were analysed in the ITT-wild-type (WT) population, 
i.e. excluding patients with EGFR mutations or ALK rearrangements. 
1 Based on the stratified log-rank test 
2 For informational purposes; in the ITT population, comparisons between Arm B and Arm C as well as 
between Arm A and Arm C were not formally tested yet as per the pre-specified analysis hierarchy 
3 Overall best response for complete response and partial response 
‡ Stratified by sex, presence of liver metastases and PD-L1 tumour expression on TC and IC 
^ The Arm C is the comparison group for all hazard ratios 
* Updated PFS analysis and interim OS analysis at clinical cut-off 22 January 2018 

   PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumours v1.1. 
   CI = confidence interval; DOR = duration of response; OS = overall survival. 
 



66 
 
 

Table 7: Summary of updated efficacy for Arm A vs. Arm B in the ITT population 
(IMpower150) 
 

Efficacy endpoint Arm A 
(Atezolizumab + 

Paclitaxel + 
Carboplatin)  

Arm B 
(Atezolizumab + 
Bevacizumab + 

Paclitaxel + Carboplatin) 
Investigator-assessed PFS (RECIST 
v1.1)* 

n = 402 n = 400 

No. of events (%) 330 (82.1%) 291 (72.8%) 
Median duration of PFS (months) 6.7 8.4 
95% CI (5.7, 6.9) (8.0, 9.9) 
Stratified hazard ratio‡^ (95% CI) 
p-value1,2 

0.67 (0.57, 0.79) 
< 0.0001 

OS interim analysis* n = 402  n = 400 
No. of deaths (%) 
Median time to events (months) 
95% CI 

206 (51.2%) 
19.5  

(16.3, 21.3) 

192 (48.0%) 
19.8 

(17.4, 24.2) 
Stratified hazard ratio‡^ (95% CI) 
p-value1,2 

0.90 (0.74, 1.10) 
0.3000 

1 Based on the stratified log-rank test 
2 For informational purposes; in the ITT population, comparisons between Arm A and Arm B were not 
included in the pre-specified analysis hierarchy 
‡ Stratified by sex, presence of liver metastases and PD-L1 expression on TC and IC 
* Updated PFS analysis and interim OS analysis at clinical cut-off 22 January 2018 
^ The Arm A is the comparison group for all hazard ratios 

 
Figure 2: Kaplan-Meier curve for overall survival in the ITT population (IMpower150) 
 

 
 



67 
 
 

Figure 3: Forest plot of overall survival by PD-L1 expression in the ITT population, Arm B vs. C 
(IMpower150) 
 

 
 
Figure 4: Kaplan-Meier curve for PFS in the ITT population (IMpower150) 
 

 
 
Figure 5: Forest plot of progression free survival by PD-L1 expression in the ITT population, 
Arm B vs. C (IMpower150)  
 

 



68 
 
 

 
In Arm B as compared to Arm C, pre-specified subgroup analyses from the interim OS analysis 
showed an OS improvement for patients with EGFR mutations or ALK rearrangements (hazard ratio 
[HR] of 0.54, 95% CI: 0.29, 1.03; median OS not reached vs. 17.5 months), and liver metastases (HR 
of 0.52, 95% CI: 0.33, 0.82; median OS 13.3 vs. 9.4 months). PFS improvements were also shown in 
patients with EGFR mutations or ALK rearrangements (HR of 0.55, 95% CI: 0.35, 0.87; median PFS 
10.0 vs. 6.1 months) and liver metastases (HR of 0.41, 95% CI: 0.26, 0.62; median PFS 8.2 vs. 5.4 
months). OS results were similar for patients aged < 65 and ≥ 65 subgroups, respectively. Data for 
patients ≥ 75 years of age are too limited to draw conclusions on this population. For all subgroup 
analyses, formal statistical testing was not planned.  
 
IMpower130 (GO29537): Randomised phase III trial in chemotherapy-naïve patients with metastatic 
non-squamous NSCLC, in combination with nab-paclitaxel and carboplatin 
 
A phase III, open-label, randomised study, GO29537 (IMpower130), was conducted to evaluate the 
efficacy and safety of atezolizumab in combination with nab-paclitaxel and carboplatin, in 
chemotherapy-naïve patients with metastatic non-squamous NSCLC. Patients with EGFR mutations or 
ALK rearrangements should have been previously treated with tyrosine kinase inhibitors. 
 
Patients were staged according to the American Joint Committee on Cancer (AJCC) 7th edition. 
Patients were excluded if they had a history of autoimmune disease, administration of live, attenuated 
vaccine within 28 days prior to randomisation, administration of immunostimulatory agents within 
4 weeks or systemic immunosuppressive medications within 2 weeks prior to randomisation, and 
active or untreated CNS metastases. Patients who had prior treatment with CD137 agonists or immune 
checkpoint blockade therapies (anti-PD-1, and anti-PD-L1 therapeutic antibodies) were not eligible. 
However, patients who had prior anti-CTLA-4 treatment could be enrolled, as long as the last dose 
was received at least 6 weeks prior to randomisation, and there was no history of severe immune-
related adverse effects from anti-CTLA-4 (NCI CTCAE Grades 3 and 4). Tumour assessments were 
conducted every 6 weeks for the first 48 weeks following Cycle 1, then every 9 weeks thereafter. 
Tumour specimens were evaluated for PD-L1 expression on tumour cells (TC) and tumour infiltrating 
immune cells (IC) and the results were used to define the PD-L1 expression subgroups for the analyses 
described below. 
 
Patients, including those with EGFR mutations or ALK rearrangements, were enrolled and were 
randomised in a 2:1 ratio to receive one of the treatment regimens described in Table 8. 
Randomisation was stratified by sex, presence of liver metastases and PD-L1 expression on TC and 
IC. Patients receiving treatment regimen B were able to crossover and receive atezolizumab 
monotherapy following disease progression. 
 
Table 8: Intravenous treatment regimens (IMpower130) 
 

Treatment  
Regimen 

Induction  
(Four or six 21-day cycles) 

Maintenance  
(21-day cycles) 

A Atezolizumab (1,200 mg)a + nab-paclitaxel 
(100 mg/m2)b,c + carboplatin (AUC 6)c  
 

Atezolizumab (1,200 mg)a 

B Nab-paclitaxel (100 mg/m2)b,c + carboplatin 
(AUC 6)c  

Best supportive care or pemetrexed 

a Atezolizumab is administered until loss of clinical benefit as assessed by investigator 
b Nab-paclitaxel is administered on days 1, 8, and 15 of each cycle 
c Nab-paclitaxel and carboplatin are administered until completion of 4-6 cycles, or progressive disease or 
unacceptable toxicity whichever occurs first 
 



69 
 
 

The demographics and baseline disease characteristics of the study population defined as ITT-WT 
(n=679) were well balanced between the treatment arms. The median age was 64 years (range 18 to 
86 years). The majority of the patients were male (59%) and white (90%). Fourteen point seven 
percent of patients had liver metastases at baseline, and most patients were current or previous 
smokers (90%). The majority of patients had a baseline ECOG performance status of 1 (59%) and PD-
L1 expression <1% (approximately 52%). Among 107 Arm B patients who had a response status of 
stable disease, partial response, or complete response after induction therapy, 40 received pemetrexed 
switch maintenance therapy.  
 
The primary analysis was conducted in all patients, excluding those with EGFR mutations or ALK 
rearrangements, defined as ITT-WT population (n=679). Patients had a median survival follow up 
time of 18.6 months and showed improved OS and PFS with atezolizumab, nab-paclitaxel and 
carboplatin as compared to the control. The key results are summarised in Table 9 and Kaplan-Meier 
curves for OS and PFS are presented in Figures 6 and 8, respectively. The exploratory results of OS 
and PFS by PD-L1 expression are summarised in Figures 7 and 9, respectively. Patients with liver 
metastases did not show improved PFS or OS with atezolizumab, nab-paclitaxel and carboplatin, 
compared to nab-paclitaxel and carboplatin (HR of 0.93, 95% CI: 0.59, 1.47 for PFS and HR of 1.04, 
95% CI: 0.63, 1.72 for OS, respectively). 
 
Fifty-nine percent of patients in the nab-paclitaxel and carboplatin arm received any cancer 
immunotherapy after disease progression, which includes atezolizumab as crossover treatment (41% 
of all patients), compared to 7.3% of patients in the atezolizumab, nab paclitaxel and carboplatin arm. 
 
In an exploratory analysis with longer follow up (median: 24.1 months), the median OS for both arms 
was unchanged relative to the primary analysis, with HR = 0.82 (95% CI: 0.67, 1.01). 
 



70 
 
 

Table 9: Summary of efficacy from IMpower130 in the primary analysis (ITT-WT population)  
 

Efficacy endpoints Arm A  
Atezolizumab + 
nab-paclitaxel + 

carboplatin 

Arm B 
Nab-paclitaxel + 

carboplatin 

Co-primary endpoints   
OS n=451 n=228 
No. of deaths (%) 226 (50.1%) 131 (57.5%) 
Median time to events (months) 18.6 13.9 
95% CI (16.0, 21.2) (12.0, 18.7) 
Stratified hazard ratio‡ (95% CI) 0.79 (0.64, 0.98) 
p-value 0.033 
12-month OS (%) 63 56 
Investigator-assessed PFS (RECIST v1.1)  n=451 n=228 
No. of events (%) 347 (76.9%) 198 (86.8%) 
Median duration of PFS (months) 7.0 5.5 
95% CI (6.2, 7.3) (4.4, 5.9) 
Stratified hazard ratio‡ (95% CI) 0.64 (0.54, 0.77) 
p-value   < 0.0001 
12-month PFS (%) 29% 14% 
  Other endpoints   
Investigator-assessed ORR (RECIST v1.1)^ n=447 n=226 
No. of confirmed responders (%) 220 (49.2%) 72 (31.9%) 
95% CI (44.5, 54.0) (25.8, 38.4) 
No. of complete response (%) 11 (2.5%) 3 (1.3%) 
No. of partial response (%) 209 (46.8%) 69 (30.5%) 
Investigator-assessed confirmed DOR (RECIST 1.1)^ n=220 n=72 
Median in months 8.4  6.1 
95% CI (6.9, 11.8) (5.5, 7.9) 

‡ Stratified by sex and PD-L1 expression on TC and IC 
^ Confirmed ORR and DoR are exploratory endpoints  
PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumours v1.1.; CI=confidence 
interval; ORR=objective response rate; DOR=duration of response; OS=overall survival 
 



71 
 
 

Figure 6: Kaplan-Meier curves for overall survival (IMpower130) 
 

 
 
Figure 7: Forest plot of overall survival by PD-L1 expression (IMpower130) 
 

 
 



72 
 
 

Figure 8: Kaplan-Meier curves for progression free survival (IMpower130) 
 

 

 
Figure 9: Forest plot of progression free survival by PD-L1 expression (IMpower130) 
 

 
 
Second-line treatment of non-small cell lung cancer 
 
OAK (GO28915): Randomised phase III trial in locally advanced or metastatic NSCLC patients 
previously treated with chemotherapy 
 
A phase III, open-label, multi-center, international, randomised study, OAK, was conducted to 
evaluate the efficacy and safety of atezolizumab compared with docetaxel in patients with locally 
advanced or metastatic NSCLC who progressed during or following a platinum-containing regimen. 
This study excluded patients who had a history of autoimmune disease, active or 
corticosteroid-dependent brain metastases, administration of a live, attenuated vaccine within 28 days 
prior to enrolment, administration of systemic immunostimulatory agents within 4 weeks or systemic 
immunosuppressive medicinal product within 2 weeks prior to enrolment. Tumour assessments were 
conducted every 6 weeks for the first 36 weeks, and every 9 weeks thereafter. Tumour specimens were 
evaluated prospectively for PD-L1 expression on tumour cells (TC) and tumour-infiltrating immune 
cells (IC). 



73 
 
 

 
A total of 1,225 patients were enrolled and per the analysis plan the first 850 randomised patients were 
included in the primary efficacy analysis. Randomisation was stratified by PD-L1 expression status on 
IC, by the number of prior chemotherapy regimens, and by histology. Patients were randomised (1:1) 
to receive either atezolizumab or docetaxel. 
 
Atezolizumab was administered as a fixed dose of 1,200 mg by intravenous infusion every 3 weeks. 
No dose reduction was allowed. Patients were treated until loss of clinical benefit as assessed by the 
investigator. Docetaxel was administered 75 mg/m2 by intravenous infusion on day 1 of each 3-week 
cycle until disease progression. For all treated patients, the median duration of treatment was 
2.1 months for the docetaxel arm and 3.4 months for the atezolizumab arm.  
 
The demographic and baseline disease characteristics of the primary analysis population were well 
balanced between the treatment arms. The median age was 64 years (range: 33 to 85), and 61% of 
patients were male. The majority of patients were white (70%). Approximately three-quarters of 
patients had non-squamous histology (74%), 10% had known EGFR mutation, 0.2% had known ALK 
rearrangements, 10% had CNS metastases at baseline, and most patients were current or previous 
smokers (82%). Baseline ECOG performance status was 0 (37%) or 1 (63%). Seventy-five percent of 
patients received only one prior platinum-based therapeutic regimen. 
 
The primary efficacy endpoint was OS. The key results of this study with a median survival follow-up 
of 21 months are summarised in Table 10. Kaplan-Meier curves for OS in the ITT population are 
presented in Figure 10. Figure 11 summarises the results of OS in the ITT and PD-L1 subgroups, 
demonstrating OS benefit with atezolizumab in all subgroups, including those with PD-L1 
expression < 1% in TC and IC.  
 



74 
 
 

Table 10: Summary of efficacy in the primary analysis population (all comers)* (OAK) 
 

Efficacy endpoint 
Atezolizumab 

(n = 425) 
Docetaxel 
(n = 425) 

Primary efficacy endpoint 
OS  
   No. of deaths (%) 271 (64%) 298 (70%) 
   Median time to events (months)  13.8 9.6 
   95% CI (11.8, 15.7) (8.6, 11.2) 

   Stratifiedǂ hazard ratio (95% CI) 0.73 (0.62, 0.87) 

   p-value** 0.0003 
12-month OS (%)*** 218 (55%) 151 (41%) 
18-month OS (%)*** 157 (40%) 98 (27%) 

Secondary endpoints 
Investigator-assessed PFS (RECIST v1.1) 
   No. of events (%) 380 (89%) 375 (88%) 
   Median duration of PFS (months) 2.8 4.0 
   95% CI (2.6, 3.0) (3.3, 4.2) 
   Stratified hazard ratio (95% CI) 0.95 (0.82, 1.10) 
Investigator-assessed ORR (RECIST v1.1) 
   No. of responders (%) 58 (14%) 57 (13%) 
   95% CI (10.5, 17.3) (10.3, 17.0) 
Investigator-assessed DOR (RECIST v1.1) n = 58 n = 57 
   Median in months 16.3 6.2 
   95% CI (10.0, NE) (4.9, 7.6) 

CI = confidence interval; DOR = duration of response; NE = not estimable; ORR = objective response rate; 
OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid 
Tumours v1.1. 
* The primary analysis population consists of the first 850 randomised patients 
ǂ Stratified by PD-L1 expression in tumour infiltrating immune cells, the number of prior chemotherapy 
regimens, and histology 
** Based on the stratified log-rank test 
*** Based on Kaplan-Meier estimates 
 



75 
 
 

Figure 10: Kaplan-Meier curve for overall survival in the primary analysis population (all 
comers) (OAK) 
 

 
 
Figure 11: Forest plot of overall survival by PD-L1 expression in the primary analysis 
population (OAK) 
 

 
 

aStratified HR for ITT and TC or IC ≥ 1%. Unstratified HR for other exploratory subgroups. 
 
An improvement in OS was observed with atezolizumab compared to docetaxel in both non-squamous 
NSCLC patients (hazard ratio [HR] of 0.73, 95% CI: 0.60, 0.89; median OS of 15.6 vs. 11.2 months 
for atezolizumab and docetaxel, respectively) and squamous NSCLC patients (HR of 0.73, 
95% CI: 0.54, 0.98; median OS of 8.9 vs. 7.7 months for atezolizumab and docetaxel, respectively). 
The observed OS improvement was consistently demonstrated across subgroups of patients including 
those with brain metastases at baseline (HR of 0.54, 95% CI: 0.31, 0.94; median OS of 20.1 
vs. 11.9 months for atezolizumab and docetaxel respectively) and patients who were never smokers 
(HR of 0.71, 95% CI: 0.47, 1.08; median OS of 16.3 vs. 12.6 months for atezolizumab and docetaxel, 



76 
 
 

respectively). However, patients with EGFR mutations did not show improved OS with atezolizumab 
compared to docetaxel (HR of 1.24, 95% CI: 0.71, 2.18; median OS of 10.5 vs. 16.2 months for 
atezolizumab and docetaxel, respectively).  
 
Prolonged time to deterioration of patient-reported pain in chest as measured by the EORTC 
QLQ-LC13 was observed with atezolizumab compared to docetaxel (HR of 0.71, 95% CI: 0.49, 1.05; 
median not reached in either arm). The time to deterioration in other lung cancer symptoms (i.e. 
cough, dyspnoea, and arm/shoulder pain) as measured by the EORTC QLQ-LC13 was similar 
between atezolizumab and docetaxel. These results should be interpreted with caution due to the open-
label design of the study. 
 
POPLAR (GO28753): Randomised phase II trial in locally advanced or metastatic NSCLC patients 
previously treated with chemotherapy 
 
A phase II, multi-centre, international, randomised, open-label, controlled study, POPLAR, was 
conducted in patients with locally advanced or metastatic NSCLC who progressed during or following 
a platinum-containing regimen, regardless of PD-L1 expression. The primary efficacy outcome was 
overall survival. A total of 287 patients were randomised 1:1 to receive either atezolizumab (1,200 mg 
by intravenous infusion every 3 weeks until loss of clinical benefit) or docetaxel (75 mg/m2 by 
intravenous infusion on day 1 of each 3-week cycle until disease progression). Randomisation was 
stratified by PD-L1 expression status on IC, by the number of prior chemotherapy regimens and by 
histology. An updated analysis with a total of 200 deaths observed and a median survival follow-up of 
22 months showed a median OS of 12.6 months in patients treated with atezolizumab, vs. 9.7 months 
in patients treated with docetaxel (HR of 0.69, 95% CI: 0.52, 0.92). ORR was 15.3% vs. 14.7% and 
median DOR was 18.6 months vs. 7.2 months for atezolizumab vs. docetaxel, respectively.  
 
Small cell lung cancer 
 
IMpower133 (GO30081): Randomised phase I/III trial in patients with chemotherapy-naïve extensive-
stage SCLC, in combination with carboplatin and etoposide 
 
A Phase I/III, randomised, multicentre, double-blind, placebo-controlled study, IMpower133, was 
conducted to evaluate the efficacy and safety of atezolizumab in combination with carboplatin and 
etoposide in patients with chemotherapy-naïve extensive-stage small cell lung cancer (ES-SCLC). 
 
Patients were excluded if they had active or untreated CNS metastases; history of autoimmune disease; 
administration of live, attenuated vaccine within 4 weeks prior to randomisation; administration of 
systemic immunosuppressive medications within 1 week prior to randomisation. Tumour assessments 
were conducted every 6 weeks for the first 48 weeks following Cycle 1, Day 1 and then every 9 weeks 
thereafter. Patients who met established criteria and who agreed to be treated beyond disease 
progression had tumour assessments conducted every 6 weeks until treatment discontinuation. 
 
A total of 403 patients were enrolled and randomised (1:1) to receive one of the treatment regimens 
described in Table 11.  Randomisation was stratified by sex, ECOG performance status, and presence 
of brain metastases.  
 



77 
 
 

Table 11: Intravenous treatment regimens (IMpower133) 
 

Treatment 
regimen 

Induction 
(Four 21-Day Cycles) 

Maintenance 
(21-Day Cycles) 

A atezolizumab (1,200 mg)a + carboplatin (AUC 5)b + 
etoposide (100 mg/m2)b,c atezolizumab (1,200 mg) a 

B placebo + carboplatin (AUC 5)b + etoposide (100 
mg/m2)b,c placebo 

a Atezolizumab was administered until loss of clinical benefit as assessed by investigator 
b Carboplatin and etoposide were administered until completion of 4 cycles, or progressive disease or 
unacceptable toxicity, whichever occurs first 
c Etoposide was administered on day 1, 2 and 3 of each cycle 
 
The demographic and baseline disease characteristics of the study population were well balanced 
between the treatment arms. The median age was 64 years (range: 26 to 90 years) with 10% of patients 
≥75 years of age. The majority of patients were male (65%), white (80%), and 9% had brain 
metastases and most patients were current or previous smokers (97%). Baseline ECOG performance 
status was 0 (35%) or 1 (65%). 
 
At the time of the primary analysis, patients had a median survival follow up time of 13.9 months. A 
statistically significant improvement in OS was observed with atezolizumab in combination with 
carboplatin and etoposide compared to the control arm (HR of 0.70, 95% CI: 0.54, 0.91; median OS of 
12.3 months vs. 10.3 months). In the exploratory OS final analysis with longer follow up (median: 
22.9 months), the median OS for both arms was unchanged relative to the primary OS interim 
analysis. The PFS, ORR and DOR results from the primary analysis as well as the exploratory OS 
final analysis results are summarised in Table 12. Kaplan-Meier curves for OS and PFS are presented 
in Figures 12 and 13. Data for patients with brain metastases are too limited to draw conclusions on 
this population.  
 



78 
 
 

Table 12: Summary of efficacy (IMpower133)  
 
Key efficacy endpoints Arm A 

(Atezolizumab + 
carboplatin + etoposide) 

Arm B 
(Placebo + carboplatin + 

etoposide) 
Co-primary endpoints   
OS analysis* n=201 n=202 
No. of deaths (%) 142 (70.6%) 160 (79.2%) 
Median time to events (months) 12.3 10.3 
95% CI (10.8, 15.8) (9.3, 11.3) 
Stratified hazard ratio‡ (95% CI) 0.76 (0.60, 0.95) 
p-value 0.0154*** 

12-month OS (%) 51.9 39.0 
Investigator-assessed PFS (RECIST v1.1) ** n=201 n=202 
No. of events (%) 171 (85.1%) 189 (93.6%) 
Median duration of PFS (months) 5.2 4.3 
95% CI (4.4, 5.6) (4.2, 4.5) 
Stratified hazard ratio‡ (95% CI) 0.77 (0.62, 0.96) 
p-value 0.0170 
6-month PFS (%) 
12-month PFS (%) 

30.9 
12.6 

22.4 
5.4 

Other endpoints   
Investigator-assessed ORR (RECIST 1.1)** ^ n=201 n=202 
No. of responders (%) 121 (60.2%) 130 (64.4%) 
95% CI (53.1, 67.0) (57.3, 71.0) 
 No. of complete response (%) 5 (2.5%) 2 (1.0%) 
 No. of partial response (%) 116 (57.7%) 128 (63.4%) 
Investigator-assessed DOR (RECIST 1.1)** ^ n =121 n = 130 
Median in months 4.2 3.9 
95% CI (4.1, 4.5) (3.1, 4.2) 
PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumours v1.1.; CI=confidence 
interval; ORR=objective response rate; DOR=duration of response; OS=overall survival 
‡ Stratified by sex and ECOG performance status  
* Exploratory OS final analysis at clinical cut-off 24 January 2019  
** PFS, ORR and DOR analyses at clinical cut-off 24 April 2018 
*** For descriptive purposes only 
^ Confirmed ORR and DoR are exploratory endpoints 
 



79 
 
 

Figure 12: Kaplan-Meier curve for overall survival (IMpower133)  
 

 
 
Figure 13: Kaplan-Meier curve for progression-free survival (IMpower133)  
 

 
 
Hepatocellular carcinoma 
 
IMbrave150 (YO40245): Randomised phase III trial in patients with unresectable HCC who have not 
received prior systemic therapy, in combination with bevacizumab  
 
A phase III, randomized, multi-center, international, open-label study, IMbrave150, was conducted to 
evaluate the efficacy and safety of atezolizumab in combination with bevacizumab, in patients with 



80 
 
 

locally advanced or metastatic and/or unresectable HCC, who have not received prior systemic 
treatment. A total of 501 patients were randomized (2:1) to receive either atezolizumab (1,200 mg) 
and 15 mg/kg of bevacizumab every 3 weeks administered by intravenous infusion, or sorafenib 
400 mg  orally twice per day. Randomization was stratified by geographic region, macrovascular 
invasion and/or extrahepatic spread, baseline α-fetoprotein (AFP) and ECOG performance status. 
Patients in both arms received treatment until loss of clinical benefit, or unacceptable toxicity. Patients 
could discontinue either atezolizumab or bevacizumab (e.g., due to adverse events) and continue on 
single-agent therapy until loss of clinical benefit or unacceptable toxicity associated with the single-
agent. 
 
The study enrolled adults whose disease was not amenable to or progressed after surgical and/or 
locoregional therapies, were Child-Pugh A, ECOG 0/1, and who had not received prior systemic 
treatment. Bleeding (including fatal events) is a known adverse reaction with bevacizumab and upper 
gastrointestinal bleeding is a common and life threatening complication in patients with HCC. Hence, 
patients were required to be evaluated for the presence of varices within 6 months prior to treatment, 
and were excluded if they had variceal bleeding within 6 months prior to treatment, untreated or 
incompletely treated varices with bleeding or high risk of bleeding. For patients with active hepatitis 
B, HBV DNA < 500 IU/mL was required within 28 days prior to initiation of study treatment, and 
standard anti-HBV treatment for a minimum of 14 days prior to study entry and for the length of 
study. 
 
Patients were also excluded if they had moderate or severe ascites; history of hepatic encephalopathy; 
known fibrolamellar HCC; sarcomatoid HCC, mixed cholangiocarcinoma and HCC; active co-
infection of HBV and HCV; history of autoimmune disease; administration of a live, attenuated 
vaccine within 4 weeks prior to randomization; administration of systemic immunostimulatory agents 
within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to randomization; 
untreated or corticosteroid-dependent brain metastases. Tumor assessments were performed every 6 
weeks for the first 54 weeks following Cycle 1, Day 1, then every 9 weeks thereafter.   
 
The demographic and baseline disease characteristics of the study population were well balanced 
between the treatment arms. The median age was 65 years (range: 26 to 88 years) and 83% were male. 
The majority of patients were Asian (57%) and white (35%). 40% were from Asia (excluding Japan), 
while 60% were from rest of world. Approximately 75% of patients presented with macrovascular 
invasion and/or extrahepatic spread and 37% had a baseline AFP ≥400 ng/mL. Baseline ECOG 
performance status was 0 (62%) or 1 (38%).  The primary risk factors for the development of HCC 
were Hepatitis B virus infection in 48% of patients, Hepatitis C virus infection in 22% of patients, and 
non-viral disease in 31% of patients. HCC was categorized as Barcelona Clinic Liver Cancer (BCLC) 
stage C in 82% of patients, stage B in 16% of patients, and stage A in 3% of patients. 
 
The co-primary efficacy endpoints were OS and IRF-assessed PFS according to RECIST v1.1. At the 
time of the primary analysis, patients had a median survival follow up time of 8.6 months. The data 
demonstrated a statistically significant improvement in OS and PFS as assessed by IRF per RECIST 
v1.1 with atezolizumab + bevacizumab compared to sorafenib.  A statistically significant improvement 
was also observed in confirmed objective response rate (ORR) by IRF per RECIST v1.1 and HCC 
modified RECIST (mRECIST). The key efficacy results are summarized in Table 13.  Kaplan-Meier 
curves for OS and PFS are presented in Figures 14 and 15. 
 



81 
 
 

Table 13: Summary of efficacy (IMbrave150) 
 

Key efficacy endpoints Atezolizumab + bevacizumab Sorafenib 
OS n=336 n=165 
No. of deaths (%) 96 (28.6%) 65 (39.4%) 
Median time to event (months)  NE  13.2 
95% CI (NE, NE) (10.4, NE) 
Stratified hazard ratio‡  (95% CI)  0.58 (0.42, 0.79) 
p-value1  0.0006 
6-month OS (%) 84.8% 72.3% 
IRF-assessed PFS, RECIST 1.1 n=336 n=165 

No. of events (%) 197 (58.6%) 109 (66.1%) 
Median duration of PFS (months) 6.8 4.3 
95% CI  (5.8, 8.3) (4.0, 5.6) 
Stratified hazard ratio‡ (95% CI) 0.59 (0.47, 0.76) 
p-value1 <0.0001 
6-month PFS 54.5% 37.2% 
IRF-assessed ORR, RECIST 
1.1 

n=326 n=159 

No. of confirmed responders (%) 89 (27.3%) 19 (11.9%) 
95% CI (22.5, 32.5) (7.4, 18.0) 
p-value2 <0.0001 
No. of complete responses (%) 18 (5.5%) 0 
No. of partial responses (%) 71 (21.8%) 19 (11.9%) 
No. of stable disease (%) 151 (46.3%) 69 (43.4%) 
IRF-assessed DOR, RECIST 
1.1 

n=89 n=19 

Median in months NE 6.3 
95% CI (NE, NE) (4.7, NE) 
Range (months) (1.3+, 13.4+) (1.4+, 9.1+) 
IRF-assessed ORR, HCC 
mRECIST  

n=325 n=158 

No. of confirmed responders (%) 108 (33.2%) 21 (13.3%) 
95% CI (28.1, 38.6) (8.4, 19.6) 
p-value2 <0.0001 
No. of complete responses (%) 33 (10.2%) 3 (1.9%) 
No. of partial responses (%) 75 (23.1%) 18 (11.4%) 
No. of stable disease (%) 127 (39.1%) 66 (41.8%) 
IRF-assessed DOR, HCC 
mRECIST  

n=108 n=21 

Median in months NE 6.3 
95% CI (NE, NE) (4.9, NE) 
Range (months) (1.3+, 13.4+) (1.4+, 9.1+) 
‡ Stratified by geographic region (Asia excluding Japan vs rest of world), macrovascular invasion and/or extrahepatic spread 
(presence vs. absence), and baseline AFP (<400 vs. ≥400 ng/mL)  
1. Based on two-sided stratified log-rank test 
2. Nominal p-values based on two-sided Cochran-Mantel-Haenszel test 
+ Denotes a censored value 
PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors v1.1; HCC mRECIST = Modified RECIST 
Assessment for Hepatocellular Carcinoma ; CI=confidence interval; ORR=objective response rate; DOR=duration of response; 
OS=overall survival; NE=not estimable 

 



82 
 
 

Figure 14: Kaplan-Meier curve for OS in the ITT population (IMbrave150) 
 

 
 
Figure 15: Kaplan-Meier curve for IRF-PFS per RECIST v1.1 in the ITT population 
(IMbrave150) 
 

 
  
Efficacy in elderly patients 
 
No overall differences in efficacy were observed between patients ≥ 65 years of age and younger 
patients receiving atezolizumab monotherapy. In study IMpower150, age ≥ 65 was associated with a 
diminished effect of atezolizumab in patients receiving atezolizumab in combination with carboplatin 
and paclitaxel.  
 
In studies IMpower150 and IMpower133, data for patients ≥75 years of age are too limited to draw 
conclusions on this population.  
 
Paediatric population 
 
An early phase, multi-centre open-label study was conducted in paediatric (<18, n=69) and young 
adult patients (18-30 years, n=18) with relapsed or progressive solid tumours as well as with 
Hodgkin’s and non-Hodgkin’s lymphoma, to evaluate the safety and pharmacokinetics of 
atezolizumab. Patients were treated with 15 mg/kg atezolizumab IV every 3 weeks (see section 5.2).  
 



83 
 
 

5.2 Pharmacokinetic properties 
 
Exposure to atezolizumab increased dose proportionally over the dose range 1 mg/kg to 20 mg/kg 
including the fixed dose 1,200 mg administered every 3 weeks. A population analysis that included 
472 patients described atezolizumab pharmacokinetics for the dose range: 1 to 20 mg/kg with a linear 
two-compartment disposition model with first-order elimination. A population pharmacokinetic 
analysis suggests that steady-state is obtained after 6 to 9 weeks (2 to 3 cycles) of repeated dosing. The 
systemic accumulation in area under the curve, maximum concentration and trough concentration was 
1.91, 1.46 and 2.75-fold, respectively. 
 
Absorption 
 
Atezolizumab is administered as an intravenous infusion. There have been no studies performed with 
other routes of administration. 
 
Distribution 
 
A population pharmacokinetic analysis indicates that central compartment volume of distribution is 
3.28 L and volume at steady-state is 6.91 L in the typical patient. 
 
Biotransformation 
 
The metabolism of atezolizumab has not been directly studied. Antibodies are cleared principally by 
catabolism. 
 
Elimination 
 
A population pharmacokinetic analysis indicates that the clearance of atezolizumab is 0.200 L/day and 
the typical terminal elimination half-life is 27 days. 
 
Special populations 
 
Based on population PK and exposure-response analyses age (21-89 years), region, ethnicity, renal 
impairment, mild hepatic impairment, level of PD-L1 expression, or ECOG performance status have 
no effect on atezolizumab pharmacokinetics. Body weight, gender, positive ADA status, albumin 
levels and tumour burden have a statistically significant, but not clinically relevant effect on 
atezolizumab pharmacokinetics. No dose adjustments are recommended. 
 
Elderly 
 
No dedicated studies of atezolizumab have been conducted in elderly patients. The effect of age on the 
pharmacokinetics of atezolizumab was assessed in a population pharmacokinetic analysis. Age was 
not identified as a significant covariate influencing atezolizumab pharmacokinetics based on patients 
of age range of 21-89 years (n=472), and median of 62 years of age. No clinically important difference 
was observed in the pharmacokinetics of atezolizumab among patients < 65 years (n=274), patients 
between 65−75 years (n=152) and patients > 75 years (n=46) (see section 4.2). 
 
Paediatric population 
 
The pharmacokinetic results from one early-phase, multi-centre open-label study that was conducted 
in paediatric (<18 years, n=69) and young adult patients (18-30 years, n=18), show that the clearance 
and volume of distribution of atezolizumab were comparable between paediatric patients receiving 
15 mg/kg and young adult patients receiving 1,200 mg of atezolizumab every 3 weeks when 
normalized by body weight, with exposure trending lower in paediatric patients as body weight 
decreased. These differences were not associated with a decrease in atezolizumab concentrations 



84 
 
 

below the therapeutic target exposure. Data for children <2 years is limited thus no definitive 
conclusions can be made. 
 
Renal impairment 
 
No dedicated studies of atezolizumab have been conducted in patients with renal impairment. In the 
population pharmacokinetic analysis, no clinically important differences in the clearance of 
atezolizumab were found in patients with mild (estimated glomerular filtration rate [eGFR] 60 to 
89 mL/min/1.73 m2; n=208) or, moderate (eGFR 30 to 59 mL/min/1.73 m2; n=116) renal impairment 
compared to patients with normal (eGFR greater than or equal to 90 mL/min/1.73 m2; n=140) renal 
function. Only a few patients had severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2; n=8) (see 
section 4.2). The effect of severe renal impairment on the pharmacokinetics of atezolizumab is 
unknown. 
 
Hepatic impairment 
 
No dedicated studies of atezolizumab have been conducted in patients with hepatic impairment. In the 
population pharmacokinetic analysis, there were no clinically important differences in the clearance of 
atezolizumab observed in patients with mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or 
bilirubin > 1.0 × to 1.5 × ULN and any AST) or moderate hepatic impairment (bilirubin > 1.5 to 3x 
ULN and any AST) in comparison to patients with normal hepatic function (bilirubin  ≤  ULN and 
AST  ≤ ULN). No data are available in patients with severe hepatic impairment (bilirubin >3 X ULN 
and any AST). Hepatic impairment was defined by the National Cancer Institute-Organ Dysfunction 
Working Group (NCI-ODWG) criteria of hepatic dysfunction (see section 4.2). The effect of severe 
hepatic impairment (bilirubin > 3 × ULN and any AST) on the pharmacokinetics of atezolizumab is 
unknown. 
 
5.3 Preclinical safety data 
 
Carcinogenicity 
 
Carcinogenicity studies have not been performed to establish the carcinogenic potential of 
atezolizumab. 
 
Mutagenicity 
 
Mutagenicity studies have not been performed to establish the mutagenic potential of atezolizumab. 
However, monoclonal antibodies are not expected to alter DNA or chromosomes.  
 
Fertility 
 
No fertility studies have been conducted with atezolizumab; however assessment of the cynomolgus 
monkey male and female reproductive organs was included in the chronic toxicity study. Weekly 
administration of atezolizumab to female monkeys at an estimated AUC approximately 6 times the 
AUC in patients receiving the recommended dose caused an irregular menstrual cycle pattern and a 
lack of newly formed corpora lutea in the ovaries which were reversible. There was no effect on the 
male reproductive organs.  
 
Teratogenicity  
 
No reproductive or teratogenicity studies in animals have been conducted with atezolizumab. Animal 
studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to immune-related 
rejection of the developing foetus resulting in foetal death. Administration of atezolizumab could 
cause foetal harm, including embryo-foetal lethality. 
 
 



85 
 
 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
L-histidine 
Glacial acetic acid 
Sucrose 
Polysorbate 20 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products except those mentioned in section 6.6. 
 
6.3 Shelf life 
 
Unopened vial 
 
3 years. 
 
Diluted solution 
 
Chemical and physical in-use stability has been demonstrated for up to 24 hours at ≤ 30 °C and for up 
to 30 days at 2 C to 8 C from the time of preparation.  
 
From a microbiological point of view, the prepared solution for infusion should be used immediately. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user and would normally not be longer than 24 hours at 2 °C to 8 °C or 8 hours at ambient temperature 
(≤ 25 °C) unless dilution has taken place in controlled and validated aseptic conditions. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C – 8 °C). 
 
Do not freeze. 
 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Type I glass vial with a butyl rubber stopper and an aluminium seal with a plastic aqua flip-off cap 
containing 20 mL of concentrate solution for infusion.  
 
Pack of one vial. 
 
6.6 Special precautions for disposal and other handling 
 
Tecentriq does not contain any antimicrobial preservative or bacteriostatic agents and should be 
prepared by a healthcare professional using aseptic technique to ensure the sterility of prepared 
solutions. 
 



86 
 
 

Aseptic preparation, handling and storage 
 
Aseptic handling must be ensured when preparing the infusion. Preparation should be:  
• performed under aseptic conditions by trained personnel in accordance with good practice rules 

especially with respect to the aseptic preparation of parenteral products.  
• prepared in a laminar flow hood or biological safety cabinet using standard precautions for the 

safe handling of intravenous agents.  
• followed by adequate storage of the prepared solution for intravenous infusion to ensure 

maintenance of the aseptic conditions. 
 
Do not shake. 
 
Instructions for dilution 
 
Twenty mL of Tecentriq concentrate should be withdrawn from the vial and diluted into a polyvinyl 
chloride (PVC), polyolefin (PO), polyethylene (PE) or polypropylene (PP) infusion bag containing 
sodium chloride 9 mg/mL (0.9%) solution for injection. After dilution, the final concentration of the 
diluted solution should be between 3.2 and 16.8 mg/mL. 
 
The bag should be gently inverted to mix the solution in order to avoid foaming. Once the infusion is 
prepared it should be administered immediately (see section 6.3). 
 
Parenteral medicinal products should be inspected visually for particulates and discolouration prior to 
administration. If particulates or discoloration are observed, the solution should not be used.  
 
No incompatibilities have been observed between Tecentriq and intravenous bags with 
product-contacting surfaces of polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or 
polypropylene (PP). In addition, no incompatibilities have been observed with in-line filter membranes 
composed of polyethersulfone or polysulfone, and infusion sets and other infusion aids composed of 
PVC, PE, polybutadiene, or polyetherurethane. The use of in-line filter membranes is optional. 
 
Do not co-administer other medicinal products through the same infusion line. 
 
Disposal  
 
The release of Tecentriq in the environment should be minimised. Any unused medicinal product or 
waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1220/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 September 2017 
 



87 
 
 

 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  

http://www.ema.europa.eu/


88 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

ANNEX II 
 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 



89 
 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
F. Hoffmann-La Roche AG 
Grenzacherstrasse 124 
4070 Basel 
SWITZERLAND 
 
Name and address of the manufacturer responsible for batch release 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
79639 Grenzach-Whylen 
GERMANY 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports (PSURs) 

 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 6 
months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.  

 



90 
 
 

• Additional risk minimisation measures 
 

Prior to launch of Tecentriq in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent 
Authority.  
 
The educational programme is aimed at increasing awareness and providing information concerning 
the signs and symptoms of certain important identified risks of atezolizumab, including immune-
related pneumonitis, hepatitis, colitis, hypothyroidism, hyperthyroidism, adrenal insufficiency, 
hypophysitis, type 1 diabetes mellitus, neuropathies, meningoencephalitis, pancreatitis, and infusion 
related reactions, and how to manage them. 
 
The MAH shall ensure that in each Member State where Tecentriq is marketed, all healthcare 
professionals and patients/carers who are expected to prescribe and use Tecentriq have access to/are 
provided with the following educational package: 
• Physician educational material 
• Patient Card 

 
The physician educational material should contain: 
• The Summary of Product Characteristics  
• Guide for healthcare professionals 

 
• The Guide for healthcare professionals shall contain the following key elements: 

- Relevant information (e.g. seriousness, severity, frequency, time to onset, reversibility as 
applicable) of the following safety concerns associated with the use of Tecentriq: 
- Immune-Related Hepatitis 
- Immune-Related Pneumonitis 
- Immune-Related Colitis 
- Immune-Related Pancreatitis 
- Immune-Related Endocrinopathies (Type 1 Diabetes Mellitus, Hypothyroidism, 

Hyperthyroidism, Adrenal Insufficiency and Hypophysitis) 
- Immune-Related Neuropathies (Guillain-Barre Syndrome, Myasthenic Syndrome / 

Myasthenia Gravis) 
- Immune-Related Meningoencephalitis 
- Immune-Related Myocarditis 
- Immune-Related Nephritis 
- Immune-Related Myositis 
- Infusion-Related Reactions 

- Description of the signs and symptoms of immune-related adverse reactions.  
- Details on how to minimise the safety concerns through appropriate monitoring and 

management. 
- Reminder to distribute the patient card to all patients receiving treatment with Tecentriq 

and to advise them to show it to any healthcare professional who may treat them.  
- Reminder to educate patients/caregivers about the symptoms of immune-related adverse 

reactions and of the need to report them immediately to the physician. 
 

The patient card shall contain the following key messages:  
• Brief introduction to atezolizumab (indication and purpose of this tool) 
• Information that atezolizumab can cause serious side effects during or after treatment, that need 

to be treated right away 
• Description of the main signs and symptoms of the following safety concerns and reminder of 

the importance of notifying their treating physician immediately if symptoms occur, persist or 
worsen: 
- Immune-Related Hepatitis 



91 
 
 

- Immune-Related Pneumonitis 
- Immune-Related Colitis 
- Immune-Related Pancreatitis 
- Immune-Related Endocrinopathies (Type 1 Diabetes Mellitus, Hypothyroidism, 

Hyperthyroidism, Adrenal Insufficiency and Hypophysitis) 
- Immune-Related Neuropathies (Guillain-Barre Syndrome, Myasthenic Syndrome / 

Myasthenia Gravis) 
- Immune-Related Meningoencephalitis 
- Immune-Related Myocarditis 
- Immune-Related Nephritis 
- Immune-Related Myositis 
- Infusion-Related Reactions 

• Warning message for patients on the importance of consulting their doctor immediately in case 
they develop any of the listed signs and symptoms and on the important not attempting to treat 
themselves.  

• Reminder to carry the Patient Card at all times and to show it to all healthcare professionals that 
may treat them. 

• The card should also prompt to enter contact details of the physician and include a warning 
message for healthcare professionals treating the patient at any time, including in conditions of 
emergency, that the patient is using Tecentriq. 

 
• Obligation to conduct post-authorisation measures 

 
The MAH shall complete, within the stated timeframe, the below measures: 
 

Description Due date 
Post-authorisation efficacy study (PAES): In order to further evaluate the efficacy of 
atezolizumab for the treatment of patients with locally advanced or metastatic 
urothelial cancer, the MAH should submit the final OS results of study IMvigor210. 

Submission of 
study results: 
31 December 
2020 

Post-authorisation efficacy study (PAES): In order to evaluate the efficacy of 
atezolizumab monotherapy versus atezolizumab plus carboplatin/gemcitabine versus 
placebo plus cisplatin/gemcitabine in patients with locally advanced or metastatic 
urothelial cancer who are platinum –ineligible and –eligible patients, the MAH should 
submit the final CSR of study IMvigor130. 

Submission of 
study results: 
31 July 2021 

 
  



92 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 

  



93 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



94 
 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tecentriq 840 mg concentrate for solution for infusion 
atezolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 14 mL vial of concentrate contains 840 mg atezolizumab 
After dilution, the final concentration of the diluted solution should be between 3.2 and 16.8 mg/mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: L-histidine, glacial acetic acid, sucrose, polysorbate 20, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
840 mg/14 mL 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Do not shake the vial 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 



95 
 
 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1220/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC  
SN  
NN 



96 
 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Tecentriq 840 mg concentrate for solution for infusion 
atezolizumab 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
For intravenous use after dilution. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
840 mg/14 mL 
 
 
6. OTHER 
 
  



97 
 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tecentriq 1,200 mg concentrate for solution for infusion 
atezolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 20 mL vial of concentrate contains 1,200 mg atezolizumab 
After dilution, the final concentration of the diluted solution should be between 3.2 and 16.8 mg/mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: L-histidine, glacial acetic acid, sucrose, polysorbate 20, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1,200 mg/20 mL 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Do not shake the vial 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 



98 
 
 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1220/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC  
SN  
NN 



99 
 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Tecentriq 1,200 mg concentrate for solution for infusion 
atezolizumab 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
For intravenous use after dilution. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1,200 mg/20 mL 
 
 
6. OTHER 
 
  



100 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 



101 
 
 

Package leaflet: Information for the patient 
 

Tecentriq 840 mg concentrate for solution for infusion 
atezolizumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how 
to report side effects. 
 
Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
 
• Keep this leaflet. You may need to read it again.  
• If you have any further questions, ask your doctor or nurse. 
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Tecentriq is and what it is used for  
2. What you need to know before you are given Tecentriq 
3. How Tecentriq is given  
4. Possible side effects  
5. How to store Tecentriq 
6. Contents of the pack and other information 
 
 
1. What Tecentriq is and what it is used for 
 
What Tecentriq is  
 
Tecentriq is an anti-cancer medicine that contains the active substance atezolizumab.  
• It belongs to a group of medicines called monoclonal antibodies.  
• A monoclonal antibody is a type of protein designed to recognise and attach to a specific target 

in the body. 
• This antibody can help your immune system fight your cancer. 
 
What Tecentriq is used for  
 
Tecentriq is used in adults to treat: 
• A kind of bladder cancer, called urothelial carcinoma 
• A kind of lung cancer, called non-small cell lung cancer 
• A kind of breast cancer, called triple negative breast cancer. 
 
Patients get Tecentriq when their cancer has spread to other parts of the body or has come back after 
previous treatment. 
 
Tecentriq may be given in combination with other anticancer medicines. It is important that you also 
read the package leaflets for the other anticancer medicines you may be receiving. If you have any 
questions about these medicines, ask your doctor. 

 



102 
 
 

How Tecentriq works 
 
Tecentriq works by attaching to a specific protein in your body called programmed death-ligand 1 
(PD-L1). This protein suppresses the body’s immune (defense) system, thereby protecting cancer cells 
from being attacked by the immune cells. By attaching to the protein, Tecentriq helps your immune 
system to fight your cancer. 
 
 
2. What you need to know before you are given Tecentriq  
 
You must not be given Tecentriq if: 
 
• you are allergic to atezolizumab or any of the other ingredients of this medicine (listed in 

section 6). 
 
If you are not sure, talk to your doctor or nurse before you are given Tecentriq. 
 
Warnings and precautions  
 
Talk to your doctor or nurse before you are given Tecentriq if you: 
• have an auto-immune disease (a condition where the body attacks its own cells) 
• have been told that your cancer has spread to your brain  
• have any history of inflammation of your lungs (called pneumonitis)  
• have or have had chronic viral infection of the liver, including hepatitis B (HBV) or hepatitis C 

(HCV) 
• have human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome 

(AIDS) 
• have had serious side effects because of other antibody therapies that help your immune system 

to fight cancer 
• have been given medicines to stimulate your immune system   
• have been given medicines to suppress your immune system 
• have been given a live, attenuated vaccine 
•        have been given medicines to treat infections (antibiotics) in the past two weeks 
 
If any of the above applies to you (or you are not sure), talk to your doctor or nurse before you are 
given Tecentriq. 
 
Tecentriq may cause some side effects that you must tell your doctor about straight away. They may 
happen weeks or months after your last dose. Tell your doctor straight away if you notice any of the 
symptoms below: 
• inflammation of the lung (pneumonitis): symptoms may include new or worsening cough, 

shortness of breath, and chest pain 
• inflammation of the liver (hepatitis): symptoms may include yellowing of skin or eyes, nausea, 

vomiting, bleeding or bruising, dark urine, and stomach pain 
• inflammation of the intestines (colitis): symptoms may include diarrhoea (watery, loose or soft 

stools), blood in stools, and stomach pain 
• inflammation of the thyroid, adrenal glands and the pituitary gland (hypothyroidism, 

hyperthyroidism, adrenal insufficiency or hypophysitis): symptoms may include tiredness, 
weight loss, weight gain, change in mood, hair loss, constipation, dizziness, headaches, 
increased thirst, increased urination and changes in vision. 

• type 1 diabetes, including acid in the blood produced from diabetes (diabetic ketoacidosis): 
symptoms may include feeling more hungry or thirsty than usual, need to urinate more often, 
weight loss, and feeling tired 



103 
 
 

• inflammation of the brain (encephalitis) or inflammation of the membrane around the spinal 
cord and brain (meningitis): symptoms may include neck stiffness, headache, fever, chills, 
vomiting, eye sensitivity to light, confusion and sleepiness  

• inflammation or problems of the nerves (neuropathy): symptoms may include muscle weakness 
and numbness, tingling in hands and feet 

• inflammation of the pancreas (pancreatitis): symptoms may include abdominal pain, nausea and 
vomiting 

• inflammation of the heart muscle (myocarditis): symptoms may include shortness of breath, 
decreased exercise tolerance, feeling tired, chest pain, swelling of the ankles or legs, irregular 
heartbeat, and fainting 

• inflammation of the kidneys (nephritis); symptoms may include changes in urine output and 
color, pain in pelvis, and swelling of the body and may lead to failure of the kidneys 

•        inflammation of the muscles (myositis); symptoms may include muscle weakness, fatigue after 
walking or standing, tripping or falling, and trouble swallowing or breathing 

• severe reactions associated with infusion (events occurring during the infusion or within one 
day of the infusion): may include fever, chills, shortness of breath and flushing. 

 
If you notice any of the symptoms above, tell your doctor straight away. 
 
Do not try to treat yourself with other medicines. Your doctor may: 
• Give you other medicines to prevent complications and reduce symptoms. 
• Delay giving your next dose of Tecentriq. 
• Stop your treatment with Tecentriq. 
 
Tests and checks 
 
Before your treatment, your doctor will check your general health. You will also have blood tests 
during your treatment. 
 
Children and adolescents 
 
This medicine should not be given to children or adolescents below 18 years of age. This is because 
the safety and efficacy of Tecentriq have not been established in this age group. 
 
Other medicines and Tecentriq 
 
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 
This includes medicines obtained without a prescription, including herbal medicines. 
 
Pregnancy and contraception 
 
• Tell your doctor if you are pregnant, think you might be pregnant or are planning to become 

pregnant. 
• You will not be given Tecentriq if you are pregnant unless your doctor considers it necessary. 

This is because the effect of Tecentriq in pregnant women is not known - it is possible that it 
could harm your unborn baby. 

• If you could become pregnant, you must use effective contraception; 
- while you are being treated with Tecentriq and  
- for 5 months after the last dose. 

• If you become pregnant while you are being treated with Tecentriq tell your doctor. 
 



104 
 
 

Breast-feeding 
 
It is not known if Tecentriq gets into breast milk. Ask your doctor if you should stop breast-feeding or 
if you should stop treatment with Tecentriq. 
 
Driving and using machines 
 
Tecentriq has minor influence on your ability to drive and use machines. If you feel tired, do not drive 
or use machines until you feel better. 
 
 
3. How Tecentriq is given 
 
You will be given Tecentriq by a doctor experienced in cancer treatment in a hospital or clinic.  
 
How much Tecentriq is given 
 
The recommended dose is either: 
• 840 milligrams (mg) every two weeks, or 
• 1,680 milligrams (mg) every four weeks. 
 
How Tecentriq is given 
 
Tecentriq is given as a drip into a vein (an intravenous infusion).  
 
Your first infusion will be given over 60 minutes.  
• Your doctor will monitor you carefully during the first infusion.  
• If you do not have an infusion reaction during the first infusion, the next infusions will be given 

to you over a period of 30 minutes.  
 
How long treatment lasts 
 
Your doctor will keep giving you Tecentriq until you no longer benefit from it. However, it may be 
stopped if the side effects become too much of a problem. 
 
If you miss a dose of Tecentriq 
 
If you miss an appointment, make another one straight away. For the treatment to be fully effective, it 
is very important to keep having the infusions.  
 
If you stop receiving Tecentriq 
 
Do not stop treatment with Tecentriq unless you have discussed this with your doctor. This is because 
stopping treatment may stop the effect of the medicine. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor straight away if you notice any of the side effects below or if they get worse. They 
may happen weeks or months after your last dose. Do not try to treat yourself with other medicines. 
 



105 
 
 

Tecentriq used alone 
 
The following side effects have been reported in clinical trials with Tecentriq used alone: 
 
Very common: may affect more than 1 in 10 people 
• fever 
• nausea 
• vomiting 
• feeling very tired with no energy (fatigue) 
• lack of energy 
• itching of the skin 
• diarrhoea 
• joint pain 
• rash 
• loss of appetite 
• shortness of breath 
• urinary tract infection 
• back pain 
• cough 
• pain in the muscles and bones 
• headache 
 
Common: may affect up to 1 in 10 people 
• inflammation of the lungs (pneumonitis) 
• low oxygen levels, which may cause shortness of breath as a consequence of inflamed lungs 

(hypoxia) 
• stomach pain 
• inflammation of the liver 
• elevated liver enzymes (shown in tests), which may be a sign of an inflamed liver  
• difficulty swallowing 
• blood tests showing low levels of potassium (hypokalaemia) or sodium (hyponatremia) 
• low blood pressure (hypotension) 
• underactive thyroid gland (hypothyroidism) 
• allergic reaction (infusion-related reaction, hypersensitivity or anaphylaxis) 
• flu-like illness 
• chills 
• inflammation of the intestines 
• low platelet count, which may make you more likely to bruise or bleed 
• blocked nose (nasal congestion) 
• high blood sugar 
• common cold 
• mouth and throat pain 
• dry skin 
• abnormal kidney test (possible kidney damage) 

 
Uncommon: may affect up to 1 in 100 people 
• inflammation of the pancreas 
• numbness or paralysis, which may be signs of Guillain-Barré syndrome 
• inflammation of the membrane around the spinal cord and brain 
• low levels of adrenal hormones 
• overactive thyroid gland (hyperthyroidism) 



106 
 
 

• type 1 diabetes 
• inflammation of muscles (myositis) 
• red, dry, scaly patches of thickened skin (psoriasis) 
 
Rare: may affect up to 1 in 1,000 people 
• inflammation of the heart muscle 
• myasthenia gravis, an illness that can cause muscle weakness 
• inflammation of the pituitary gland situated at the base of the brain 
• inflammation of the kidneys 
• inflammation of the eye (uveitis) 
 
Tecentriq used in combination with anticancer medicines 
 
The following side effects have been reported in clinical trials when Tecentriq is given in combination 
with anticancer medicines: 
 
Very common: may affect more than 1 in 10 people 
• low number of red blood cells, which can cause tiredness and shortness of breath 
• low white blood cell count with and without fever, which can increase the risk of infection 

(neutropenia, leukopenia) 
• low platelet count, which may make you more likely to bruise or bleed (thrombocytopenia) 
• constipation 
• nerve damage resulting in possible numbness, pain, and/or loss of motor function (peripheral 

neuropathy) 
• underactive thyroid gland (hypothyroidism) 
• loss of appetite 
• shortness of breath 
• diarrhoea 
• nausea 
• itching of the skin 
• rash 
• joint pain 
• feeling very tired (fatigue)  
• fever 
• headache 
• cough 
• pain in the muscles and bones 
• vomiting 
• back pain 
• lack of energy 
• infection of the lung 
• hair loss 
• high blood pressure (hypertension) 
• swelling in arms or legs 
 
Common: may affect up to 1 in 10 people 
• blood tests showing low levels of potassium (hypokalaemia) or sodium (hyponatremia) 
• inflammation of the mouth or lips 
• hoarse voice (dysphonia) 
• low levels of magnesium (hypomagnesaemia), which can cause weakness and muscle cramping, 

numbness and pain in the arms and legs 
• protein in urine (proteinuria) 
• fainting 



107 
 
 

• elevated liver enzymes (shown in tests), which may be a sign of an inflamed liver 
• changes to sense of taste (dysgeusia) 
• decreased number of lymphocyte (a type of white blood cells), which is associated with an    

increased risk of infection 
• abnormal kidney test (possible kidney damage) 
• overactive thyroid gland (hyperthyroidism) 
• dizziness 
• infusion-related reactions 
•        severe infection in the blood (sepsis) 
 
Uncommon: may affect up to 1 in 100 people 
• red, dry, scaly patches of thickened skin (psoriasis) 
 
If you notice any of the side effects above or if they get worse, tell your doctor straight away. 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Tecentriq 
 
Tecentriq will be stored by the healthcare professionals at the hospital or clinic. The storage details are 
as follows: 
• Do not use this medicine after the expiry date which is stated on the carton and the vial label 

after EXP. The expiry date refers to the last day of that month.  
• Store in a refrigerator (2 °C - 8 °C). Do not freeze. 
• Keep the vial in the outer carton in order to protect from light. 
• The diluted solution should not be kept more than 24 hours at 2 °C to 8 °C or 8 hours at ambient 

temperature (≤ 25 °C), unless dilution has taken place in controlled and validated aseptic 
conditions. 

• Do not use if this medicine is cloudy, discoloured or contains particles 
 
Do not throw away any medicines via wastewater or household waste. Your healthcare professional 
will throw away any medicines that are no longer being used. These measures will help to protect the 
environment. 
 
 
6. Contents of the pack and other information 
 
What Tecentriq contains  
 
• The active substance is atezolizumab. Each mL contains 60 mg of atezolizumab.  

Each 14 mL vial contains 840 mg of atezolizumab. 
• After dilution, the final concentration of the diluted solution should be between 3.2 and 

16.8 mg/mL. 
• The other ingredients are L-histidine, glacial acetic acid, sucrose, polysorbate 20 and water for 

injections. 
 
What Tecentriq looks like and contents of the pack 
 
Tecentriq is a concentrate for solution for infusion. It is a clear, colourless to slightly yellowish liquid.  

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


108 
 
 

 
Tecentriq is available in a pack containing 1 glass vial. 
 
Marketing Authorisation Holder 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
Manufacturer 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 
Grenzach-Wyhlen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. O. 
Tel: +420 - 2 20382111 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s 
Tlf: +45 - 36 39 99 99 
  

Malta 
(See Ireland) 
 

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140  

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 177 380  
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Ελλάδα 
Roche (Hellas) A.E. 
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 

France 
Roche 
Tél: +33 (0) 1 47 61 40 00 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 



109 
 
 

  
Hrvatska 
Roche d.o.o. 
Tel: +385 1 4722 333 
 
Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 
Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland 
Roche a/s 
c/o Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika 
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy 
Puh/Tel: +358 (0) 10 554 500 
 

Κύπρος 
Γ.Α.Σταμάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 6 7039831 
 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

 
This leaflet was last revised in {MM/YYYY}. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 

http://www.ema.europa.eu/


110 
 
 

--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Instructions for dilution 
 
For the recommended dose of 840 mg: fourteen mL of Tecentriq concentrate should be withdrawn 
from the vial and diluted into a polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or 
polypropylene (PP) infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection. 
 
For the recommended dose of 1680 mg: twenty-eight mL of Tecentriq concentrate should be 
withdrawn from two vials of Tecentriq 840 mg and diluted into a polyvinyl chloride (PVC), polyolefin 
(PO), polyethylene (PE), or polypropylene (PP) infusion bag containing sodium chloride 9 mg/mL 
(0.9%) solution for injection. 
 
After dilution, the final concentration of the diluted solution should be between 3.2 and 16.8 mg/mL. 
 
The bag should be gently inverted to mix the solution in order to avoid foaming. Once the infusion is 
prepared it should be administered immediately. 
 
Parenteral medicinal products should be inspected visually for particulates and discolouration prior to 
administration. If particulates or discoloration are observed, the solution should not be used.  
 
No incompatibilities have been observed between Tecentriq and intravenous bags with 
product-contacting surfaces of polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or 
polypropylene (PP). In addition, no incompatibilities have been observed with in-line filter membranes 
composed of polyethersulfone or polysulfone, and infusion sets and other infusion aids composed of 
PVC, PE, polybutadiene, or polyetherurethane. The use of in-line filter membranes is optional. 
 
Diluted solution 
 
Chemical and physical in-use stability has been demonstrated for up to 24 hours at ≤ 30 °C and for up 
to 30 days at 2°C to 8°C from the time of preparation.  
 
From a microbiological point of view, the prepared solution for infusion should be used immediately. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user and would normally not be longer than 24 hours at 2 °C to 8 °C or 8 hours at ambient temperature 
(≤ 25 °C), unless dilution has taken place in controlled and validated aseptic conditions. 
 
Method of administration  
 
Tecentriq is for intravenous use. The infusions must not be administered as an intravenous push or 
bolus. 
 
The initial dose of Tecentriq must be administered over 60 minutes. If the first infusion is well 
tolerated all subsequent infusions may be administered over 30 minutes. 
 
Do not co-administer other medicinal products through the same infusion line. 
 
Disposal 
 
The release of Tecentriq in the environment should be minimised. Any unused medicinal product or 
waste material should be disposed of in accordance with local requirements. 



111 
 
 

Package leaflet: Information for the patient 
 

Tecentriq 1,200 mg concentrate for solution for infusion 
atezolizumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how 
to report side effects. 
 
Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
 
• Keep this leaflet. You may need to read it again.  
• If you have any further questions, ask your doctor or nurse. 
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Tecentriq is and what it is used for  
2. What you need to know before you are given Tecentriq 
3. How Tecentriq is given  
4. Possible side effects  
5. How to store Tecentriq 
6. Contents of the pack and other information 
 
 
1. What Tecentriq is and what it is used for 
 
What Tecentriq is  
 
Tecentriq is an anti-cancer medicine that contains the active substance atezolizumab.  
• It belongs to a group of medicines called monoclonal antibodies.  
• A monoclonal antibody is a type of protein designed to recognise and attach to a specific target 

in the body. 
• This antibody can help your immune system fight your cancer.  
 
What Tecentriq is used for  
 
Tecentriq is used in adults to treat: 
• A kind of bladder cancer, called urothelial carcinoma 
• A kind of lung cancer, called non-small cell lung cancer 
• A kind of lung cancer, called small cell lung cancer 
•        A kind of liver cancer, called hepatocellular carcinoma 
 
Patients get Tecentriq when their cancer has spread to other parts of the body or has come back after 
previous treatment. 
 
Tecentriq may be given in combination with other anticancer medicines. It is important that you also 
read the package leaflets for the other anticancer medicines you may be receiving. If you have any 
questions about these medicines, ask your doctor. 
 



112 
 
 

How Tecentriq works 
 
Tecentriq works by attaching to a specific protein in your body called programmed death-ligand 1 
(PD-L1). This protein suppresses the body’s immune (defense) system, thereby protecting cancer cells 
from being attacked by the immune cells. By attaching to the protein, Tecentriq helps your immune 
system to fight your cancer. 
 
 
2. What you need to know before you are given Tecentriq  
 
You must not be given Tecentriq if: 
 
• you are allergic to atezolizumab or any of the other ingredients of this medicine (listed in 

section 6). 
 
If you are not sure, talk to your doctor or nurse before you are given Tecentriq. 
 
Warnings and precautions  
 
Talk to your doctor or nurse before you are given Tecentriq if you: 
• have an auto-immune disease (a condition where the body attacks its own cells) 
• have been told that your cancer has spread to your brain  
• have any history of inflammation of your lungs (called pneumonitis)  
• have or have had chronic viral infection of the liver, including hepatitis B (HBV) or hepatitis C 

(HCV) 
• have human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome 

(AIDS) 
• have had serious side effects because of other antibody therapies that help your immune system 

to fight cancer 
• have been given medicines to stimulate your immune system   
• have been given medicines to suppress your immune system 
• have been given a live, attenuated vaccine 
•        have been given medicines to treat infections (antibiotics) in the past two weeks 
 
If any of the above applies to you (or you are not sure), talk to your doctor or nurse before you are 
given Tecentriq. 
 
Tecentriq may cause some side effects that you must tell your doctor about straight away. They may 
happen weeks or months after your last dose. Tell your doctor straight away if you notice any of the 
symptoms below: 
• inflammation of the lung (pneumonitis): symptoms may include new or worsening cough, 

shortness of breath, and chest pain 
• inflammation of the liver (hepatitis): symptoms may include yellowing of skin or eyes, nausea, 

vomiting, bleeding or bruising, dark urine, and stomach pain 
• inflammation of the intestines (colitis): symptoms may include diarrhoea (watery, loose or soft 

stools), blood in stools, and stomach pain 
• inflammation of the thyroid, adrenal glands and the pituitary gland (hypothyroidism, 

hyperthyroidism, adrenal insufficiency or hypophysitis): symptoms may include tiredness, 
weight loss, weight gain, change in mood, hair loss, constipation, dizziness, headaches, 
increased thirst, increased urination and changes in vision. 

• type 1 diabetes, including acid in the blood produced from diabetes (diabetic ketoacidosis): 
symptoms may include feeling more hungry or thirsty than usual, need to urinate more often, 
weight loss, and feeling tired 



113 
 
 

• inflammation of the brain (encephalitis) or inflammation of the membrane around the spinal 
cord and brain (meningitis): symptoms may include neck stiffness, headache, fever, chills, 
vomiting, eye sensitivity to light, confusion and sleepiness  

• inflammation or problems of the nerves (neuropathy): symptoms may include muscle weakness 
and numbness, tingling in hands and feet 

• inflammation of the pancreas (pancreatitis): symptoms may include abdominal pain, nausea and 
vomiting 

• inflammation of the heart muscle (myocarditis): symptoms may include shortness of breath, 
decreased exercise tolerance, feeling tired, chest pain, swelling of the ankles or legs, irregular 
heartbeat, and fainting 

• inflammation of the kidneys (nephritis); symptoms may include changes in urine output and 
color, pain in pelvis, and swelling of the body and may lead to failure of the kidneys 

•        inflammation of the muscles (myositis); symptoms may include muscle weakness, fatigue after 
walking or standing, tripping or falling, and trouble swallowing or breathing 

• severe reactions associated with infusion (events occurring during the infusion or within one 
day of the infusion): may include fever, chills, shortness of breath and flushing. 

 
If you notice any of the symptoms above, tell your doctor straight away. 
 
Do not try to treat yourself with other medicines. Your doctor may: 
• Give you other medicines to prevent complications and reduce symptoms. 
• Delay giving your next dose of Tecentriq. 
• Stop your treatment with Tecentriq. 
 
Tests and checks 
 
Before your treatment, your doctor will check your general health. You will also have blood tests 
during your treatment. 
 
Children and adolescents 
 
This medicine should not be given to children or adolescents below 18 years of age. This is because 
the safety and efficacy of Tecentriq have not been established in this age group. 
 
Other medicines and Tecentriq 
 
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 
This includes medicines obtained without a prescription, including herbal medicines. 
 
Pregnancy and contraception 
 
• Tell your doctor if you are pregnant, think you might be pregnant or are planning to become 

pregnant. 
• You will not be given Tecentriq if you are pregnant unless your doctor considers it necessary. 

This is because the effect of Tecentriq in pregnant women is not known - it is possible that it 
could harm your unborn baby. 

• If you could become pregnant, you must use effective contraception; 
- while you are being treated with Tecentriq and  
- for 5 months after the last dose. 

• If you become pregnant while you are being treated with Tecentriq tell your doctor. 
 



114 
 
 

Breast-feeding 
 
It is not known if Tecentriq gets into breast milk. Ask your doctor if you should stop breast-feeding or 
if you should stop treatment with Tecentriq. 
 
Driving and using machines 
 
Tecentriq has minor influence on your ability to drive and use machines. If you feel tired, do not drive 
or use machines until you feel better. 
 
 
3. How Tecentriq is given 
 
You will be given Tecentriq by a doctor experienced in cancer treatment in a hospital or clinic.  
 
How much Tecentriq is given 
 
The recommended dose is 1,200 milligrams (mg) every three weeks. 
 
How Tecentriq is given 
 
Tecentriq is given as a drip into a vein (an intravenous infusion).  
 
Your first infusion will be given over 60 minutes.  
• Your doctor will monitor you carefully during the first infusion.  
• If you do not have an infusion reaction during the first infusion, the next infusions will be given 

to you over a period of 30 minutes.  
 
How long treatment lasts 
 
Your doctor will keep giving you Tecentriq until you no longer benefit from it. However, it may be 
stopped if the side effects become too much of a problem. 
 
If you miss a dose of Tecentriq 
 
If you miss an appointment, make another one straight away. For the treatment to be fully effective, it 
is very important to keep having the infusions.  
 
If you stop receiving Tecentriq 
 
Do not stop treatment with Tecentriq unless you have discussed this with your doctor. This is because 
stopping treatment may stop the effect of the medicine. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor straight away if you notice any of the side effects below or if they get worse. They 
may happen weeks or months after your last dose. Do not try to treat yourself with other medicines. 
 
Tecentriq used alone 
 
The following side effects have been reported in clinical trials with Tecentriq used alone: 



115 
 
 

 
Very common: may affect more than 1 in 10 people 
• fever 
• nausea 
• vomiting 
• feeling very tired with no energy (fatigue) 
• lack of energy 
• itching of the skin 
• diarrhoea 
• joint pain 
• rash 
• loss of appetite 
• shortness of breath 
• urinary tract infection 
• back pain 
• cough 
• pain in the muscles and bones 
• headache 
 
Common: may affect up to 1 in 10 people 
• inflammation of the lungs (pneumonitis) 
• low oxygen levels, which may cause shortness of breath as a consequence of inflamed lungs 

(hypoxia) 
• stomach pain 
• inflammation of the liver 
• elevated liver enzymes (shown in tests), which may be a sign of an inflamed liver  
• difficulty swallowing 
• blood tests showing low levels of potassium (hypokalaemia) or sodium (hyponatremia) 
• low blood pressure (hypotension) 
• underactive thyroid gland (hypothyroidism) 
• allergic reaction (infusion-related reaction, hypersensitivity or anaphylaxis) 
• flu-like illness 
• chills 
• inflammation of the intestines 
• low platelet count, which may make you more likely to bruise or bleed 
• blocked nose (nasal congestion) 
• high blood sugar 
• common cold 
• mouth and throat pain 
• dry skin 
• abnormal kidney test (possible kidney damage) 

 
Uncommon: may affect up to 1 in 100 people 
• inflammation of the pancreas 
• numbness or paralysis, which may be signs of Guillain-Barré syndrome 
• inflammation of the membrane around the spinal cord and brain 
• low levels of adrenal hormones 
• overactive thyroid gland (hyperthyroidism) 
• type 1 diabetes 
• inflammation of muscles (myositis) 
• red, dry, scaly patches of thickened skin (psoriasis) 
 



116 
 
 

Rare: may affect up to 1 in 1,000 people 
• inflammation of the heart muscle 
• myasthenia gravis, an illness that can cause muscle weakness 
• inflammation of the pituitary gland situated at the base of the brain 
• inflammation of the kidneys 
• inflammation of the eye (uveitis) 
 
Tecentriq used in combination with anticancer medicines 
 
The following side effects have been reported in clinical trials when Tecentriq is given in combination 
with anticancer medicines: 
 
Very common: may affect more than 1 in 10 people 
• low number of red blood cells, which can cause tiredness and shortness of breath 
• low white blood cell count with and without fever, which can increase the risk of infection 

(neutropenia, leukopenia) 
• low platelet count, which may make you more likely to bruise or bleed (thrombocytopenia) 
• constipation 
• nerve damage resulting in possible numbness, pain, and/or loss of motor function (peripheral 

neuropathy) 
• underactive thyroid gland (hypothyroidism) 
• loss of appetite 
• shortness of breath 
• diarrhoea 
• nausea 
• itching of the skin 
• rash 
• joint pain 
• feeling very tired (fatigue) 
• fever 
• headache 
• cough 
• pain in the muscles and bones 
• vomiting 
• back pain 
• lack of energy 
• infection of the lung 
• hair loss 
• high blood pressure (hypertension) 
• swelling in arms or legs 

 
Common: may affect up to 1 in 10 people 
• blood tests showing low levels of potassium (hypokalaemia) or sodium (hyponatremia) 
• inflammation of the mouth or lips 
• hoarse voice (dysphonia) 
• low levels of magnesium (hypomagnesaemia), which can cause weakness and muscle cramping, 

numbness and pain in the arms and legs 
• protein in urine (proteinuria) 
• fainting 
• elevated liver enzymes (shown in tests), which may be a sign of an inflamed liver 
• changes to sense of taste (dysgeusia) 
• decreased number of lymphocyte (a type of white blood cells), which is associated with an 

increased risk of infection 



117 
 
 

• abnormal kidney test (possible kidney damage) 
• overactive thyroid gland (hyperthyroidism) 
• dizziness 
• infusion-related reactions 
•        severe infection in the blood (sepsis) 
 
Uncommon: may affect up to 1 in 100 people 
• red, dry, scaly patches of thickened skin (psoriasis) 
 
If you notice any of the side effects above or if they get worse, tell your doctor straight away. 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Tecentriq 
 
Tecentriq will be stored by the healthcare professionals at the hospital or clinic. The storage details are 
as follows: 
• Do not use this medicine after the expiry date which is stated on the carton and the vial label 

after EXP. The expiry date refers to the last day of that month.  
• Store in a refrigerator (2 °C - 8 °C). Do not freeze. 
• Keep the vial in the outer carton in order to protect from light. 
• The diluted solution should not be kept more than 24 hours at 2 °C to 8 °C or 8 hours at ambient 

temperature (≤ 25 °C), unless dilution has taken place in controlled and validated aseptic 
conditions. 

• Do not use if this medicine is cloudy, discoloured or contains particles 
 
Do not throw away any medicines via wastewater or household waste. Your healthcare professional 
will throw away any medicines that are no longer being used. These measures will help to protect the 
environment. 
 
 
6. Contents of the pack and other information 
 
What Tecentriq contains  
 
• The active substance is atezolizumab. Each mL contains 60 mg of atezolizumab.  

Each vial contains 1,200 mg of atezolizumab (in 20 mL). 
• After dilution, the final concentration of the diluted solution should be between 3.2 and 

16.8 mg/mL. 
• The other ingredients are L-histidine, glacial acetic acid, sucrose, polysorbate 20 and water for 

injections. 
 
What Tecentriq looks like and contents of the pack 
 
Tecentriq is a concentrate for solution for infusion. It is a clear, colourless to slightly yellowish liquid.  
 
Tecentriq is available in a pack containing 1 glass vial. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


118 
 
 

Marketing Authorisation Holder 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
Manufacturer 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 
Grenzach-Wyhlen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. O. 
Tel: +420 - 2 20382111 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s 
Tlf: +45 - 36 39 99 99 
  

Malta 
(See Ireland) 
 

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140  

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 177 380  
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Ελλάδα 
Roche (Hellas) A.E. 
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 

France 
Roche 
Tél: +33 (0) 1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 
 



119 
 
 

Hrvatska 
Roche d.o.o. 
Tel: +385 1 4722 333 
 
Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 
Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland 
Roche a/s 
c/o Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika 
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy 
Puh/Tel: +358 (0) 10 554 500 
 

Κύπρος 
Γ.Α.Σταμάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 6 7039831 
 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

 
This leaflet was last revised in {MM/YYYY}. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 

http://www.ema.europa.eu/


120 
 
 

--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Instructions for dilution 
 
Twenty mL of Tecentriq concentrate should be withdrawn from the vial and diluted into a polyvinyl 
chloride (PVC), polyolefin (PO), polyethylene (PE), or polypropylene (PP) infusion bag containing 
sodium chloride 9 mg/mL (0.9%) solution for injection. After dilution, the final concentration of the 
diluted solution should be between 3.2 and 16.8 mg/mL. The bag should be gently inverted to mix the 
solution in order to avoid foaming. Once the infusion is prepared it should be administered 
immediately. 
 
Parenteral medicinal products should be inspected visually for particulates and discolouration prior to 
administration. If particulates or discoloration are observed, the solution should not be used.  
 
No incompatibilities have been observed between Tecentriq and intravenous bags with 
product-contacting surfaces of polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or 
polypropylene (PP). In addition, no incompatibilities have been observed with in-line filter membranes 
composed of polyethersulfone or polysulfone, and infusion sets and other infusion aids composed of 
PVC, PE, polybutadiene, or polyetherurethane. The use of in-line filter membranes is optional. 
 
Diluted solution 
 
Chemical and physical in-use stability has been demonstrated for up to 24 hours at ≤ 30 °C and for up 
to 30 days at 2 °C to 8 °C from the time of preparation.  
 
From a microbiological point of view, the prepared solution for infusion should be used immediately. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user and would normally not be longer than 24 hours at 2 °C to 8 °C or 8 hours at ambient temperature 
(≤ 25 °C), unless dilution has taken place in controlled and validated aseptic conditions. 
 
Method of administration  
 
Tecentriq is for intravenous use. The infusions must not be administered as an intravenous push or 
bolus. 
 
The initial dose of Tecentriq must be administered over 60 minutes. If the first infusion is well 
tolerated all subsequent infusions may be administered over 30 minutes. 
 
Do not co-administer other medicinal products through the same infusion line. 
 
Disposal 
 
The release of Tecentriq in the environment should be minimised. Any unused medicinal product or 
waste material should be disposed of in accordance with local requirements. 

 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET