natgillin/translations-raw huggingface dataset:
CHF blev rapporteret i op til 3, 5% af patienterne, som behandledes med Avastin, sammenlignet med 0, 9% i kontrolgruppen.
CHF was reported in up to 3.5% of patients treated with Avastin compared with up to 0.9% in the control arms.
De fleste af patienterne udviste symptombedring og/ eller forbedring af venstre ventrikels funktion efter passende medicinsk behandling.
Most of these patients showed improved symptoms and/ or left ventricular function following appropriate medical therapy.
I de fleste af de kliniske studier med Avastin blev patienter med præ- eksisterende CHF (New York Heart Association) (NYHA II- IV) ekskluderet, og derfor findes der ingen data for risikoen for CHF i denne population.
In most clinical trials of Avastin, patients with pre-existing CHF of NYHA (New York Heart Association (NYHA) II-IV were excluded, therefore, no information is available on the risk of CHF in this population.
Tidligere eksponering for anthracykliner og/ eller strålebehandling af brystvæggen kan være mulige risikofaktorer for udvikling af CHF.
Prior anthracyclines exposure and/ or prior radiation to the chest wall may be possible risk factors for the development of CHF.
Ældre patienter Randomiserede, kliniske studier viste at alder > 65 år var associeret med øget risiko for udvikling af arterielle tromboemboliske hændelser, inklusive cerebrovaskulære tilfælde, transitorisk iskæmisk anfald og myokardieinfarkt.
Elderly Patients In randomised clinical trials, age > 65 years was associated with an increased risk of developing arterial thromboembolic events, including cerebrovascular accidents (CVAs), transient ischaemic attacks (TIAs) and myocardial infarctions (MIs).
Andre reaktioner med en højere frekvens, der blev set hos patienter over 65 år, var grad 3- 4 leukopeni og trombocytopeni og neutropeni (alle grader), diarre, kvalme, hovedpine og træthed i forhold til patienter under 65 år i behandling med Avastin (se pkt 4. 4 og 4. 8 under Tromboemboli).
Other reactions with a higher frequency seen in patients over 65 were grade 3-4 leucopenia and thrombocytopenia; and all grade neutropenia, diarrhoea, nausea, headache and fatigue as compared to those aged ≤ 65 years when treated with Avastin (see sections 4.4 and 4.8 under Thromboembolism).
Hos ældre patienter (> 65 år) som modtog Avastin, var der ingen forhøjet incidens af Avastin - relaterede hændelser, inklusive gastrointestinal perforation, sårhelingskomplikationer, hypertension, proteinuri, kongestiv hjertesygdom og blødninger, sammenlignet med patienter under 65 år, som modtog Avastin.
No increase in the incidence of other reactions, including gastrointestinal perforation, wound healing complications, hypertension, proteinuria, congestive heart failure, and haemorrhage was observed in elderly patients (> 65 years) receiving Avastin as compared to those aged ≤ 65 years treated with Avastin.
Laboratorieabnormaliteter:
Laboratory Abnormalities:
11 Hos de patienter, der blev behandlet med Avastin, er der fra kliniske undersøgelser set en stigning på mindst 2% i hyppigheden af følgende grad 3 eller 4- laboratorieabnormaliteter sammenlignet med kontrolgrupperne:
Across clinical trials, the following Grade 3 and 4 laboratory abnormalities occurred in patients treated with Avastin with at least a 2% difference compared to the corresponding control groups:
Hyperglykæmi, nedsat hæmoglobin, hypokaliæmi, hyponatriæmi, nedsat antal hvide blodceller, stigning i international normaliseret ratio (INR).
11 hyperglycaemia, decreased haemoglobin, hypokalaemia, hyponatraemia, decreased white blood cell count, increased international normalised ratio (INR).
Post- marketing efaring:
Post-marketing experience:
Bivirkninger rapporteret post- marketing
Adverse reactions reported in post-marketing setting
Bivirkninger (frekvens *)
Reactions (frequency*)
Hypertensiv encephalopati
Nervous system disorders
4. 4 Særlige
Hypertensive encephalopathy (very rare) (see also section 4.4 Special warnings and precautions for use, and Hypertension in section 4.8 Undesirable Effects)
advarsler og forsigtighedsregler vedrørende brugen) og “ Hypertension ” i 4. 8 Bivirkninger) Reversibel Posterior Leukoencephalopathy Syndrome (sjælden) (se også pkt 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen)
Reversible Posterior Leukoencephalopathy Syndrome (rare) (see also section 4.4 Special warnings and precautions for use)
Renal thrombotisk mikroangiopati, som manifesterer sig som proteinuri (ukendt frekvens).
Renal Thrombotic Microangiopathy, clinically manifested as proteinuria (frequency not known).
For yderligere information om proteinuri se pkt 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen og ” Proteinuri ” i pkt.
For further information on proteinuria see section 4.4 Special warnings and precautions for use, and Proteinuria in section 4.8 Undesirable Effects.
4. 8 Bivirkninger
Respiratory, thoracic and mediastinal
Luftveje, thorax og mediastinum
Nasal septum perforation (not known)
Nasal septum- perforation (ukendt) Pulmonær hypertension (ukendt) Dysfoni (almindelig)
Pulmonary hypertension (not known)
* Hvis frekvensen findes, er den udledt af data fra kliniske forsøg
Dysphonia (common) * if specified, the frequency has been derived from clinical trial data
Den højeste dosis, som blev afprøvet på mennesker (20 mg/ kg legemsvægt, intravenøst hver 14. dag), var forbundet med svær migræne hos flere patienter.
The highest dose tested in humans (20 mg/ kg of body weight, intravenous every 2 weeks) was associated with severe migraine in several patients.
Antineoplastiske lægemidler, monoklonale antistoffer, ATC- kode:
Antineoplastic agents, monoclonal antibody, ATC code:
Virkningsmekanisme Bevacizumab binder sig til vascular endothelial growth factor (VEGF), som er den primære faktor i vasculogenesen og angiogenesen og hæmmer derved bindingen af VEGF til dets receptorer, Flt- 1 (VEGFR- 1) og KDR (VEGFR- 2), på overfladen af endothelceller.
Mechanism of action Bevacizumab binds to vascular endothelial growth factor (VEGF), the key driver of vasculogenesis and angiogenesis, and thereby inhibits the binding of VEGF to its receptors, Flt-1 (VEGFR-1) and KDR (VEGFR-2), on the surface of endothelial cells.
Neutralisering af VEGF’ s biologiske aktivitet hæmmer vaskulariseringen af tumorer, normaliserer den tilbageblevne tumorvaskulatur, hæmmer dannelsen af ny tumorvaskulatur og hæmmer derved tumorvæksten.
Neutralising the biological activity of VEGF regresses the vascularisation of tumours, normalises remaining tumour vasculature, and inhibits the formation of new tumour vasculature, thereby inhibiting tumour growth.
Farmakodynamiske virkninger Administration af bevacizumab eller dets parenterale, murine antistof til nøgne mus i xenotransplantationsmodeller af kræft medførte omfattende anti- tumor aktivitet ved humane kræftformer, inklusive colon, mamma -, pancreas - og prostatakræft.
Pharmacodynamic effects Administration of bevacizumab or its parental murine antibody to xenotransplant models of cancer in nude mice resulted in extensive anti-tumour activity in human cancers, including colon, breast, pancreas and prostate.
12 Klinisk effekt
12 Clinical efficacy
Metastatisk carcinom i kolon eller rektum
Metastatic carcinoma of the colon or rectum (mCRC)
Sikkerhed og effekt af den anbefalede dosis (5 mg/ kg legemsvægt hver 2. uge) hos patienter med metastatisk kolorektalkræft blev undersøgt i tre randomiserede, aktivt kontrollerede kliniske studier i kombination med fluoropyrimidinbaseret 1. linje- kemoterapi.
The safety and efficacy of the recommended dose (5 mg/ kg of body weight every two weeks) in metastatic carcinoma of the colon or rectum were studied in three randomised, active-controlled clinical trials in combination with fluoropyrimidine-based first-line chemotherapy.
Et ugentligt regime med irinotecan/ bolus af 5- fluorouracil/ folinsyre (IFL- regime) i 4 uger i hver 6 ugers cyklus (Salz- regimet) ● AVF0780g:
A weekly schedule of irinotecan/ bolus 5-fluorouracil/ folinic acid (IFL) for a total of 4 weeks of each 6 week-cycle (Saltz regimen). • AVF0780g:
I kombination med en bolus af 5- fluorouracil/ folinsyre (5- FU/ FA) i 6 uger i hver 8 ugers cyklus (Roswell Park regimet) ● AVF2192g:
In combination with bolus 5-fluorouracil/ folinic acid (5-FU/ FA) for a total of 6 weeks of each 8 week-cycle (Roswell Park regimen). • AVF2192g:
I kombination med en bolus af 5- FU/ FA i 6 uger i hver 8 ugers cyklus (Roswell Park regimet) hos patienter som ikke var optimale kandidater til 1. linje behandling med irinotecan.
In combination with bolus 5-FU/ FA for a total of 6 weeks of each 8 week-cycle (Roswell Park regimen) in patients who were not optimal candidates for first-line irinotecan treatment.
To yderligere studier blev udført i 1. linje (NO16966) og 2. linje (E3200) behandling af metastatisk carcinom i kolon eller rektum med Avastin i følgende doseringer, i kombination med FOLFOX- 4 (5FU/ LV/ oxaliplatin) og XELOX (capecitabin/ oxaliplatin):
Two additional studies were conducted in first (NO16966) and second line (E3200) treatment of metastatic carcinoma of the colon or rectum, with Avastin administered in the following dosing regimens, in combination with FOLFOX-4 (5FU/ LV/ Oxaliplatin) and XELOX (Capecitabine/ Oxaliplatin):
● NO16966:
• NO16966:
Avastin 7, 5 mg/ kg legemsvægt hver 3. uge i kombination med oral capecitabin og intravenøs oxaliplatin (XELOX) eller Avastin 5 mg/ kg hver 2. uge i kombination med leucovorin plus 5- fluorouracil bolus efterfulgt af 5- fluorouracil infusion og intravenøs oxaliplatin (FOLFOX- 4).
Avastin 7.5 mg/ kg of body weight every 3 weeks in combination with oral capecitabine and intravenous oxaliplatin (XELOX) or Avastin 5 mg/ kg every 2 weeks in combination with leucovorin plus 5-fluorouracil bolus, followed by 5-fluorouracil infusion, with intravenous oxaliplatin (FOLFOX-4).
● E3200:
• E3200:
Avastin 10 mg/ kg legemsvægt hver 2. uge i kombination med leucovorin og 5 - fluorouracil bolus, efterfulgt af 5- fluorouracil infusion og intravenøs oxaliplatin (FOLFOX- 4).
Avastin 10 mg/ kg of body weight every 2 weeks in combination with leucovorin and 5-fluorouracil bolus, followed by 5-fluorouracil infusion, with intravenous oxaliplatin (FOLFOX-4).
Studiet var et randomiseret, dobbeltblindet, aktivt kontrolleret, klinisk fase III studie, som evaluerede Avastin i kombination med IFL som førstelinje behandling af metastatisk kolorektalkræft.
This was a phase III randomised, double-blind, active-controlled clinical trial evaluating Avastin in combination with IFL as first-line treatment for metastatic carcinoma of the colon or rectum.
Der blev randomiseret 813 patienter til behandling med IFL + placebo (arm 1) eller IFL + Avastin (5 mg/ kg hver 2. uge, arm 2).
Eight hundred and thirteen patients were randomised to receive IFL + placebo (Arm 1) or IFL + Avastin (5 mg/ kg every 2 weeks, Arm 2).
En tredje gruppe på 110 patienter fik en bolus af 5- FU/ FA + Avastin (arm 3).
A third group of 110 patients received bolus 5-FU/ FA+Avastin (Arm3).
Inklusionen i arm 3 blev stoppet som forud planlagt, da sikkerheden af Avastin med IFL- regimet var dokumenteret og blev anset for acceptabel.
Enrollment in Arm 3 was discontinued, as pre-specified, once safety of Avastin with the IFL regimen was established and considered acceptable.
Den samlede gennemsnitsalder var 59, 4 år, 56, 6% af patienterne havde en ECOG performance status på 0, 43% havde en status på 1 og 0, 4% havde en status på 2.
The overall mean age was 59.4 years; 56.6% of patients had an ECOG performance status of 0, 43% had a value of 1 and 0.4% had a value of 2.
15, 5% havde tidligere modtaget strålebehandling og 28, 4% havde tidligere modtaget kemoterapi.
15.5% had received prior radiotherapy and 28.4% prior chemotherapy.
Tillæg af Avastin til IFL resulterede i en signifikant stigning i den samlede overlevelse, progressionsfri overlevelse og samlet responsrate (se tabel 3).
The addition of Avastin to IFL resulted in statistically significant increases in overall survival, progression-free survival and overall response rate (see Table 3).
Den kliniske gevinst, bedømt efter samlet overlevelse, blev set i alle forudspecificerede patientundergrupper, inklusive grupper defineret iht. alder, køn, performance status, lokalisering af primær tumor, antal involverede organer og varighed af metastatisk sygdom.
The clinical benefit, as measured by overall survival, was seen in all pre-specified patient subgroups, including those defined by age, sex, performance status, location of primary tumour, number of organs involved and duration of metastatic disease.
Resultaterne for effekt af Avastin i kombination med IFL- kemoterapi fremgår af tabel 3.
The efficacy results of Avastin in combination with IFL-chemotherapy are displayed in Table 3.
13 Tabel 3
13 Table 3
Resultater for effekt i studie AVF2107g
Efficacy results for study AVF2107g
Arm 1 IFL + Placebo
Arm 1
Arm 2 IFL + Avastina
Arm 2
Antal patienter
Number of Patients Overall survival
95% konfidensinterval b
95% Confidence Interval b
14, 29- 16, 99
14.29 – 16.99
18, 46- 24, 18
18.46 – 24.18
Hazard ratio
Hazard ratio
0, 660
0.660
(p- værdi = 0, 00004) Progressionsfri overlevelse
(p-value = 0.00004) Progression-free survival
Median tid (måneder) Hazard ratio
Median time (months) Hazard ratio
(p- værdi < 0, 0001) Samlet responsrate a
Overall response rate
Rate (%)
Rate (%)
mg/ kg hver 2. uge
5 mg/ kg every 2 weeks.
forhold til kontrolarmen
(p-value = 0.0036)
Blandt de 110 patienter randomiseret til arm 3 (5- FU/ FA + Avastin) inden lukning af denne arm, var den mediane samlede overlevelse 18, 3 måneder og den mediane progressionsfri overlevelse var 8, 8 måneder.
Among the 110 patients randomised to Arm 3 (5-FU/ FA + Avastin) prior to discontinuation of this arm, the median overall survival was 18.3 months and the median progression free survival was 8.8 months.
Studiet var et randomiseret, dobbeltblindet, aktivt kontrolleret, klinisk fase II studie, som undersøgte effekt og sikkerhed af Avastin i kombination med 5- FU/ FA som førstelinje behandling af metastatisk kolorektalkræft hos patienter som ikke var optimale kandidater for førstelinje behandling med irinotecan.
This was a phase II randomised, double-blind, active-controlled clinical trial evaluating the efficacy and safety of Avastin in combination with 5-FU/ FA as first-line treatment for metastatic colorectal cancer in patients who were not optimal candidates for first-line irinotecan treatment.
Der blev randomiseret 105 patienter til 5- FU/ FA + placebo- armen og 104 patienter til 5- FU/ FA + Avastin- armen (5 mg/ kg hver 2. uge).
One hundred and five patients were randomised to 5-FU/ FA + placebo arm and 104 patients to 5-FU/ FA + Avastin (5 mg/ kg every 2 weeks) arm.
Sammenlignet med 5- FU/ FA- kemoterapi alene medførte tillæg af Avastin 5 mg/ kg hver 2. uge til 5- FU/ FV en højere, objektive responsrater, signifikant længere progressionsfri overlevelse og en tendens til længere overlevelse.
The addition of Avastin 5 mg/ kg every two weeks to 5-FU/ FA resulted in higher objective response rates, significantly longer progression-free survival, and a trend in longer survival as compared to 5-FU/ FA chemotherapy alone.
Studiet var et åbent, randomiseret, aktivt kontrolleret, klinisk fase II studie som undersøgte Avastin i kombination med 5- FU/ FA som førstelinje behandling af metastatisk kolorektalkræft.
This was a phase II randomised, active-controlled, open-labelled clinical trial investigating Avastin in combination with 5-FU/ FA as first-line treatment of metastatic colorectal cancer.
19% af patienterne havde tidligere modtaget kemoterapi og 14% havde tidligere modtaget strålebehandling.
19% of the patients had received prior chemotherapy and 14% prior radiotherapy.
Der blev randomiseret 71 patienter til bolus 5- FU/ FA eller 5- FU/ FA + Avastin (5 mg/ kg hver 2. uge).
Seventy-one patients were randomised to receive bolus 5-FU/ FA or 5-FU/ FA + Avastin (5 mg/ kg every 2 weeks).
En tredje gruppe på 33 patienter fik bolus 5- FU/ FA + Avastin (10 mg/ kg hver 2. uge).
A third group of 33 patients received bolus 5-FU/ FA + Avastin (10 mg/ kg every 2 weeks).
Det primære endpoint for forsøget var objektiv responsrate og progressionsfri overlevelse.
The primary endpoints of the trial were objective response rate and progression-free survival.
Sammenlignet med 5- FU/ FA- kemoterapi alene medførte tillæg af Avastin 5 mg/ kg hver 2. uge til 5- FU/ FA en højere, objektiv responsrate, længere progressionsfri overlevelse og en tendens til længere overlevelse (se tabel 4).
The addition of Avastin 5 mg/ kg every two weeks to 5-FU/ FA resulted in higher objective response rates, longer progression-free survival, and a trend in longer survival, compared with 5-FU/ FA chemotherapy alone (see Table 4).
Disse effektdata er konsistente med resultaterne fra studie AVF2107g.
These efficacy data are consistent with the results from study AVF2107g.
Effektdata fra studierne AVF0780g og AVF2192g som undersøgte Avastin i kombination med 5- FU/ FA- kemoterapi er sammenfattet i tabel 4.
The efficacy data from studies AVF0780g and AVF2192g investigating Avastin in combination with 5-FU/ FA-chemotherapy are summarised in Table 4.
14 Tabel 4:
14 Table 4:
Resultater for effekt fra studierne AVF0780g og AVF2192g
Efficacy results for studies AVF0780g and AVF2192g
Antal patienter Samlet overlevelse
Number of Patients Overall survival
13. 6
13.6
17. 7 15. 2 12. 9
17.7 15.2 12.9
16. 6
16.6
95% konfidensinterval c
95% Confidence Interval c
10. 35 - 16. 95
10.35 - 16.95
13. 63 - 19. 32
13.63 – 19.32
P- værdi
p-value
Median tid (måneder) Hazard ratio
Median time (months)
5, 2
9.2
9, 0 0, 44
Hazard ratio
7, 2 0, 69
0.44
5, 5
0.69
9, 2 0, 5
0.5
P
p
- værdi -
-value -
95% konfidensinterval p- værdi
95% CI
11, 7 - 42, 6 0, 43
11.7 – 42.6
9, 2 - 23, 9
9.2 - 23.9
- 35, 6 0, 055
0.055
Responsvarighed
Duration of response
25- 75 percentil (måneder)
25– 75 percentile (months)
5, 5 − NR
5.5 − NR
6, 1 − NR
6.1 − NR
3, 8 - 7, 8
3.8 – 7.8
5, 59 - 9, 17
5.59 - 9.17
5, 88 - 13, 01
5.88 - 13.01
mg/ kg hver 2. uge.
mg/ kg every 2 weeks.
10 mg/ kg hver 2. uge. c I forhold til kontrolarmen.
10 mg/ kg every 2 weeks. c Relative to control arm.
(XELOX) administreret hver 3. uge blev undersøgt i forhold til Avastin 5 mg/ kg i kombination med leucovorin med 5- fluorouracil bolus efterfulgt 5- fluorouracil infusion og i. v. oxaliplatin (FOLFOX- 4), administreret hver 2. uge.
NO16966 This was a phase III randomised, double-blind (for bevacizumab), clinical trial investigating Avastin 7.5 mg/ kg in combination with oral capecitabine and IV oxaliplatin (XELOX), administered on a 3- weekly schedule; or Avastin 5 mg/ kg in combination with leucovorin with 5-fluorouracil bolus, followed by 5-fluorouracil infusional, with IV oxaliplatin (FOLFOX-4), administered on a 2-weekly schedule.
Studiet bestod af to dele: en initial, ublindet 2 - armet del (del 1) hvor patienterne blev randomiseret til to forskellige behandlingsgrupper (XELOX og FOLFOX- 4) og en efterfølgende 2 x 2 4- armet del (del 2), hvor patienterne blev randomiseret til fire behandlingsgrupper (XELOX + placebo, FOLFOX - 4 + placebo, XELOX + Avastin, FOLFOX- 4 + Avastin).
The study contained two parts: an initial unblinded 2-arm part (Part I) in which patients were randomised to two different treatment groups (XELOX and FOLFOX-4) and a subsequent 2 x 2 factorial 4-arm part (Part II) in which patients were randomised to four treatment groups (XELOX + placebo, FOLFOX-4 + placebo, XELOX + Avastin, FOLFOX-4 + Avastin).
Omkring 350 patienter blev randomiseret i hver af de 4 behandlingsarme i del 2 af forsøget.
Approximately 350 patients were randomised into each of the 4 study arms in the Part II of the trial.
15 Tabel 5
15 Table 5
Behandlingsregimer i studie N016966 (mCRC)
Treatment Regimens in Study N016966 (mCRC)
Behandling Startdosis
Treatment Starting Dose
FOLFOX- 4 eller
FOLFOX-4
Oxaliplatin Leucovorin
Oxaliplatin
85 mg/ m2 iv 2 h 2 200 mg/ m iv 2 h
85 mg/ m2 IV 2 h 2
Oxaliplatin på dag 1 Leucovorin på dag 1 og 2
Oxaliplatin on Day 1
Avastin
or
5- Fluorouracil
Leucovorin
400 mg/ m2 iv bolus, 600 mg / m2 iv 22 h
200 mg/ m IV 2 h
dag 1 og 2
Leucovorin on Day 1 and 2
Placebo eller Avastin
5-Fluorouracil Placebo or Avastin
5 mg/ kg iv 30- 90 min
400 mg/ m2 IV bolus, 600 mg/ m2 IV 22 h 5 mg/ kg IV 30-90 min
Dag 1 før FOLFOX- 4, hver 2. uge
5-fluorouracil IV bolus/ infusion, each on Days 1 and 2 Day 1, prior to FOLFOX-4, every 2 weeks
XELOX eller
XELOX
130 mg/ m2 iv 2 h 2 1000 mg/ m oral to
130 mg/ m2 IV 2 h 2
Oxaliplatin på dag 1 Oral capecitabin to gange daglig i 2
Oxaliplatin on Day 1
gange daglig
Capecitabine
uger (efterfulgt af 1 uge uden behandling)
Capecitabine oral bid for 2 weeks (followed by 1 week off treatment)
7. 5 mg/ kg iv 30- 90 min
7.5 mg/ kg IV 30-90 min
iv bolus injektion umiddelbart efter leucovorin
IV bolus injection immediately after leucovorin
Den primære effektparameter for forsøget var varigheden af progressionsfri overlevelse.
The primary efficacy parameter of the trial was the duration of progression-free survival.
At vise at XELOX var non- inferior i forhold til FOLFOX- 4 og at vise at Avastin i kombination med FOLFOX- 4 eller XELOX kemoterapi var bedre i forhold til kemoterapi alene.
In this study, there were two primary objectives: to show that XELOX was non-inferior to FOLFOX-4 and to show that Avastin in combination with FOLFOX-4 or XELOX chemotherapy was superior to chemotherapy alone.
XELOX- armene, var non- inferior med hensyn til progressionsfri overlevelse og samlet overlevelse i den egnede ” per protocol ” patientpopulation i forhold til FOLFOX- 4 armene
Non-inferiority of the XELOX-containing arms compared with the FOLFOX-4-containing arms in the overall comparison was demonstrated in terms of progression-free survival and overall survival in the eligible per-protocol population.
Avastinarmene var bedre med hensyn til progressionsfri overlevelse i ITT (intent- to- treat) populationen (tabel 6) i forhold til behandlingsarmene, der kun indeholdt kemoterapi
Superiority of the Avastin-containing arms versus the chemotherapy alone arms in the overall comparison was demonstrated in terms of progression-free survival in the ITT population (Table 6)
Resultatet er konsistent med den statistiske signifikante fordel, som blev observeret i den samlede analyse.
Secondary PFS analyses, based on ‘ on-treatment’ -based response assessments, confirmed the significantly superior clinical benefit for patients treated with Avastin (analyses shown in Table 6), consistent with the statistically significant benefit observed in the pooled analysis.
16 Tabel 6
16 Table 6
Nøgletal for effektresultater af superioritets- analysen
Key efficacy results for the superiority analysis
(ITT population, studie NO16966)
(ITT population, Study NO16966)
Endpoint (måneder)
Endpoint (months)
p- værdi
P Value
Primære endpoint
Primary endpoint
eller XELOX + placebo (n=701)
+ Placebo (n=701)
eller XELOX + bevacizumab (n=699)
Bevacizumab (n=699)
Median PFS **
Median PFS**
Hazard ratio (97, 5% CI)
Hazard ratio (97.5% CI)a
Sekundære endpoints
Secondary endpoints
Median PFS (i behandling) **
Median PFS (on treatment)**
Hazard ratio (97, 5% CI)
Hazard ratio (97.5% CI)
Samlet responsrate (Invest.
Overall response rate (Invest.
Assessment) **
Assessment)**
Median samlet overlevelse *
Median overall survival*
* Samlet overlevelsesanalyse ved klinisk cut- off 31. januar 2007 ** Primær analyse ved klinisk cut- off 31. januar 2006 a I forhold til kontrolarmen
* Overall survival analysis at clinical cut-off 31 January 2007 ** Primary analysis at clinical cut-off 31 January 2006 a relative to control arm
7, 4 måneder vs 9, 3 måneder, HR=0, 77; 97, 5%.
In the FOLFOX treatment subgroup, the median PFS was 8.6 months in placebo and 9.4 months in bevacizumab treated patients, HR = 0.89, 97.5% CI = [0.73; 1.08]; p-value = 0.1871, the corresponding results in the XELOX treatment subgroup being 7.4 vs.
Konfidensinterval = [0, 63; 0, 94]; p- værdien = 0, 0026.
9.3 months, HR = 0.77, 97.5% CI = [0.63; 0.94]; p-value = 0.0026.