BRAIN: trial | Bending the Curve: Trial by Trial

BRAIN

Bevacizumab alone or in combination with irinotecan in recurrent glioblastoma (BRAIN, AVF3708g)

Population

Patients with recurrent glioblastoma; 167 randomly assigned

Design

Randomised, multicentre, open-label, noncomparative phase 2 trial: bevacizumab 10 mg/kg alone or with irinotecan (340 mg/m2 or 125 mg/m2, with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks; primary endpoints 6-month progression-free survival and objective response rate by independent radiology review; secondary endpoints safety and overall survival

Primary endpoint

ORR, PFS

Arms

Bevacizumab alone (experimental): Bevacizumab 10 mg/kg once every 2 weeks
Bevacizumab plus irinotecan (experimental): Bevacizumab 10 mg/kg plus irinotecan (340 mg/m2 or 125 mg/m2) once every 2 weeks

People

Friedman HS

Show the numbers

Results reported for BRAIN
Endpoint	Analysis	Bevacizumab alone / Bevacizumab plus irinotecan	Control	Effect
ORRRandomly assigned patients (n=167); analysis population not stated in the abstractObjective response rate as determined by independent radiology review	primaryFriedman 2009	28.2%	—	Noncomparative design: the trial did not test one arm against the other, and the abstract gives no confidence intervals.
PFSRandomly assigned patients (n=167); analysis population not stated in the abstractEstimated progression-free survival rate at 6 months as determined by independent radiology review	primaryFriedman 2009	42.6% at 6 mo	—	—
OSRandomly assigned patients (n=167); analysis population not stated in the abstract	primaryFriedman 2009	median 9.2 months	—	Secondary endpoint; no confidence intervals or hazard ratio in the abstract.

Results reported for BRAIN
Endpoint	Analysis	Bevacizumab alone / Bevacizumab plus irinotecan	Control	Effect
ORRRandomly assigned patients (n=167); analysis population not stated in the abstractObjective response rate as determined by independent radiology review	primaryFriedman 2009	28.2%	—	Noncomparative design: the trial did not test one arm against the other, and the abstract gives no confidence intervals.
PFSRandomly assigned patients (n=167); analysis population not stated in the abstractEstimated progression-free survival rate at 6 months as determined by independent radiology review	primaryFriedman 2009	42.6% at 6 mo	—	—
OSRandomly assigned patients (n=167); analysis population not stated in the abstract	primaryFriedman 2009	median 9.2 months	—	Secondary endpoint; no confidence intervals or hazard ratio in the abstract.

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Bevacizumab alone (experimental)
Bevacizumab plus irinotecan (experimental)

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

Data table (modelled values)

Months	Bevacizumab alone	Bevacizumab plus irinotecan
0	100.0%	100.0%
6	63.6%	62.0%
12	40.5%	38.4%
17	27.8%	25.8%
23	17.7%	16.0%

Appears in

2009 Bevacizumab approved for progressive glioblastoma on response rate

Sources

Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733-40.
PubMed DOI