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AVAglio

Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma (AVAglio)

Phase 3NCT00943826

Population
Patients with newly diagnosed supratentorial glioblastoma; 458 assigned to bevacizumab and 463 to placebo
Design
Randomised phase 3 trial of intravenous bevacizumab (10 mg/kg every 2 weeks) or placebo plus radiotherapy (2 Gy 5 days a week; maximum 60 Gy) and daily temozolomide (75 mg/m2) for 6 weeks, then after a 28-day break maintenance bevacizumab or placebo plus temozolomide (150 to 200 mg/m2 for 5 days) for six 4-week cycles, then bevacizumab 15 mg/kg every 3 weeks or placebo until progression or unacceptable toxicity; coprimary endpoints investigator-assessed progression-free survival and overall survival
Primary endpoint
PFS, OS
Arms
  • Bevacizumab plus radiotherapy-temozolomide (experimental, n = 458): Bevacizumab 10 mg/kg every 2 weeks with radiotherapy and temozolomide, then maintenance bevacizumab with temozolomide, then bevacizumab monotherapy
  • Placebo plus radiotherapy-temozolomide (control, n = 463): Placebo with radiotherapy and temozolomide, then maintenance placebo with temozolomide, then placebo
People
Chinot OL
PFSHR 0.64 (95% CI 0.55–0.74)Δ median PFS+4.4 monthsOSHR 0.88 (95% CI 0.76–1.02)Δ 12-month OS+6.1 points
Show the numbers
Results reported for AVAglio
EndpointAnalysisBevacizumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomideEffect
PFSRandomly assigned patients (n=458 and n=463); analysis population not stated in the abstractInvestigator-assessed progression-free survival (coprimary endpoint)primaryChinot 2014median 10.6 monthsmedian 6.2 monthsHR 0.64 (95% CI 0.55–0.74)P<0.001Stratified hazard ratio for progression or death.
OSRandomly assigned patients (n=458 and n=463); analysis population not stated in the abstractOverall survival (coprimary endpoint)primaryChinot 201472.4% at 12 mo; 33.9% at 2 y66.3% at 12 mo; 30.1% at 2 yHR 0.88 (95% CI 0.76–1.02)P=0.10Stratified hazard ratio for death; the abstract reports no significant difference. Survival at 1 year: P=0.049; at 2 years: P=0.24. Medians are not given in the abstract.
Results reported for AVAglio
EndpointAnalysisBevacizumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomideEffect
PFSRandomly assigned patients (n=458 and n=463); analysis population not stated in the abstractInvestigator-assessed progression-free survival (coprimary endpoint)primaryChinot 2014median 10.6 monthsmedian 6.2 monthsHR 0.64 (95% CI 0.55–0.74)P<0.001Stratified hazard ratio for progression or death.
OSRandomly assigned patients (n=458 and n=463); analysis population not stated in the abstractOverall survival (coprimary endpoint)primaryChinot 201472.4% at 12 mo; 33.9% at 2 y66.3% at 12 mo; 30.1% at 2 yHR 0.88 (95% CI 0.76–1.02)P=0.10Stratified hazard ratio for death; the abstract reports no significant difference. Survival at 1 year: P=0.049; at 2 years: P=0.24. Medians are not given in the abstract.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.640.55–0.74
OS0.880.76–1.02
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Bevacizumab plus radiotherapy-temozolomide (experimental)
  • Placebo plus radiotherapy-temozolomide (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsBevacizumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomide
0100.0%100.0%
763.3%45.7%
1342.7%23.4%
2027.0%10.7%
2717.1%4.9%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Bevacizumab plus radiotherapy-temozolomide (experimental)
  • Placebo plus radiotherapy-temozolomide (control)
Data table (modelled values)
MonthsBevacizumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomide
0100.0%100.0%
686.9%83.3%
1369.6%63.4%
1950.5%45.3%
2633.9%30.1%
Primary publication: Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709-22. PubMedDOI

Appears in

Sources

  1. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709-22.

    PubMedDOI