A Study Investigating the Outcomes and Safety of Atezolizumab Under Real-World Conditions in Patients Treated in Routine Clinical Practice

Study Overview
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Brief Summary
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This is a non-interventional, multi-country, multi-centre, multiple cohort prospective study, with retrospective collection of prior medical/treatment history data from medical records, designed to assess the real-world outcomes and safety of atezolizumab for indications in the existing label in the real world setting of routine clinical practice.

Detailed Description
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The study will be split into separate cohorts based on the approved indications for atezolizumab treatment, excluding cisplatin ineligible participants receiving atezolizumab as first line of therapy (LOT1) for locally advanced/metastatic urothelial cancer (locally advanced/metastatic UC). The study may be amended for inclusion of new cohorts as these are approved in the participating countries. Participants will be included into each cohort based on their indication for receiving atezolizumab.

Official Title
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A Non-Interventional, Multicenter, Multiple Cohort Study Investigating the Outcomes and Safety of Atezolizumab Under Real-World Conditions in Patients Treated in Routine Clinical Practice

Conditions
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Urothelial Carcinoma, Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Atezolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have one of the following confirmed diagnoses for which atezolizumab is locally approved in the SmPC: (1) As monotherapy for the treatment of adult patients with locally advanced/metastatic UC after prior platinum-containing chemotherapy (Cohort 1 LOT2+mUC) or (2) As monotherapy for the treatment of adult patients with locally advanced/metastatic NSCLC after prior chemotherapy. Patients with EGFR activating mutations or ALK-positive tumour mutations should also have received targeted therapy before receiving atezolizumab (Cohort 2 LOT2+NSCLC) or (3) In combination with bevacizumab, paclitaxel and carboplatin for the first line treatment of adult patients with metastatic non-squamous NSCLC. Patients with EGFR activating mutations or ALK- positive tumour mutations should also have received targeted therapy (Cohort 3 LOT1 NSCLC) or (4) 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) (Cohort 4 LOT1 ES-SCLC) or (5) As a monotherapy, for the treatment of metastatic NSCLC with high PD-L1 expression, previously untreated (Cohort 5 LOT1 NSCLC) or (6) In combination with bevacizumab for unresectable locally advanced or metastatic hepatocellular carcinoma previously untreated with systemic therapy (Cohort 6 LOT1 HCC) . Patient is administered atezolizumab therapy for the first time. Decision to administer atezolizumab must be made and documented prior to inclusion into the study and must follow local clinical practice. Exclusion Criteria: Patients not receiving treatment for a disease with atezolizumab according to standard of care and in line with the current summary of product characteristics (SPC) or local labelling. Cisplatin ineligible patients receiving atezolizumab LOT1 for the treatment of locally advanced/metastatic UC patients will be excluded Concomitant anti-cancer therapy at the time of starting atezolizumab on the index date not part of locally approved combination therapy with atezolizumab. Treatment with atezolizumab as part of a clinical trial or for compassionate use as part of a pre-approval or compassionate use program. Patients not receiving atezolizumab, but a biosimilar or non-original biologic.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1 (UC LOT2+later lines[LOT2+] & platinum eligible LOT1)<br>Participants diagnosed with locally advanced or metastatic Urothelial Cancer previously treated with platinum-containing chemotherapy. Enrollment is closed. | Drug: Atezolizumab<br>* Atezolizumab will be administered at the discretion of the treating physician per local guidelines and independently of participation in this study.<br>* Other names: Tecentriq;|
| Cohort 2 (NSCLC LOT2 plus later lines [LOT2+])<br>Participants diagnosed with Locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) after prior chemotherapy. Participants with epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK)-positive tumor mutations should also have received targeted therapy. Enrollment closed. | Drug: Atezolizumab<br>* Atezolizumab will be administered at the discretion of the treating physician per local guidelines and independently of participation in this study.<br>* Other names: Tecentriq;|
| Cohort 3 (NSCLC LOT1 plus EGFR+/ALK+ LOT2+)<br>EMA: Participants diagnosed with locally advanced/metastatic non-squamous NSCLC not previously treated. Participants with EGFR-activating mutations or ALK-positive tumor mutations should have received at least one line of targeted therapy. FDA: for the treatment of adult participants with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Participants with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving TECENTRIQ. Enrollment is closed. | Drug: Atezolizumab<br>* Atezolizumab will be administered at the discretion of the treating physician per local guidelines and independently of participation in this study.<br>* Other names: Tecentriq;|
| Cohort 4 (ES-SCLC LOT1)<br>Participants diagnosed with extensive stage (ES) small cell lung cancer (SCLC) not previously treated. Enrollment is closed. | Drug: Atezolizumab<br>* Atezolizumab will be administered at the discretion of the treating physician per local guidelines and independently of participation in this study.<br>* Other names: Tecentriq;|
| Cohort 5 (NSCLC LOT1)<br>Participants diagnosed with metastatic Non-Small Cell Lung cancer with high PD-L1 expression, previously untreated. | Drug: Atezolizumab<br>* Atezolizumab will be administered at the discretion of the treating physician per local guidelines and independently of participation in this study.<br>* Other names: Tecentriq;|
| Cohort 6 (HCC LOT1)<br>Participants diagnosed with unresectable locally advanced or metastatic hepatocellular carcinoma previously untreated with systemic therapy. | Drug: Atezolizumab<br>* Atezolizumab will be administered at the discretion of the treating physician per local guidelines and independently of participation in this study.<br>* Other names: Tecentriq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time from index date until date of death from any cause. Index date is the date of administration of the first ever dose of atezolizumab for each patient. | Index date up to approximately 6 years | 
| OS at 2 Years | Percentage of participants alive 2 years after initiation of atezolizumab treatment. | After index date up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Loss of Clinical Benefit (TTLCB) | Time from the index date to loss of clinical benefit as assessed by the treating physician. | Index date up to approximately 6 years | 
| Progression Free Survival (PFS) | Time from index date to death or disease progression (PD). | Index date up to approximately 6 years | 
| Objective Response Rate (ORR) | Percentage of participants who have a best overall response (BOR) of Complete Response (CR) or Partial Response (PR). BOR for each participant is the best response achieved after the index date prior to initiation of any subsequent treatment. | After index date up to approximately 6 years | 
| Time to Response | Time from index date to first objective tumor response, CR or PR. | Index date up to approximately 6 years | 
| Duration of Response (DoR) | Time from first documentation of CR or PR (whichever occurs first) after index until death or PD. | Index date up to approximately 6 years | 
| Disease Control Rate (DCR) | Percentage of participants who have achieved CR, PR and stable disease at least 12 weeks after the index date. | From 12 weeks after index date up to approximately 6 years | 
| Duration of DCR | Time from first documentation of CR, PR or stable disease (whichever occurs first) after index until death or PD. | After index date up to approximately 6 years | 
| EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Score | EQ-5D-5L during and after atezolizumab treatment will be used to assess HRQoL. Scale is from 1-5 (no problems, slight problems, moderate problems, severe problems and extreme problems). | Index date or after ICF signature, & approx. at 6, 12, and 24 weeks of treatment; then at approx. 3 months, 6 months, 12 months, & every 12 months thereafter until end of study (study planned duration up to approximately 6 years) | 
| Number of Paricipants with Disease Stage TNM and IUCC |  | At index date (Index date is the date of administration of the first ever dose of atezolizumab for each patient.) | 
| Number of Participants at Each Level of Karnofsky or ECOG Performance Status |  | At index date (Index date is the date of administration of the first ever dose of atezolizumab for each patient. | 
| Total Number of Infusions of Atezolizuamb |  | Treatment period until discontinuation (up to approximately 6 years) | 
| Duration of Treatment With Atezolizumab |  | Index date until date of treatment discontinuation (up to approximately 6 years) | 
| Time to initiation of the first subsequent cancer-related therapy |  | Up to approximately 6 years | 
| Percentage of Participants with Adverse Events |  | Up to approximately 6 years | 
| Number of Lines of Prior and Subsequent Cancer-Related Therapies |  | Up to approximately 6 years |