On May 5, 2009, the U.S. Food and Drug Administration granted accelerated approval to
bevacizumab injection (
Avastin; Genentech, Inc., South San Francisco, CA) as a single agent for patients with
glioblastoma multiforme (GBM) with progressive disease following prior
therapy. The approval was based on durable objective responses (independent radiologic review with stable or decreasing
corticosteroid use). Two trials evaluating
bevacizumab, 10 mg/kg by i.v. infusion every 2 weeks, were submitted. One trial also randomized patients to
bevacizumab plus
irinotecan treatment. All patients had received prior surgery,
radiotherapy, and
temozolomide. Patients with active
brain hemorrhage were excluded. One trial enrolled 78 independently confirmed GBM patients. Partial responses were observed in 25.9% (95% confidence interval [CI], 17.0%-36.1%) of the patients. The median response duration was 4.2 months (95% CI, 3.0-5.7 months). The second trial enrolled 56 GBM patients. Partial responses were observed in 19.6% (95% CI, 10.9%-31.3%) of the patients. The median response duration was 3.9 months (95% CI, 2.4-17.4 months). Safety data were provided for the first study. The most frequently reported
bevacizumab adverse events of any grade were
infection,
fatigue,
headache,
hypertension,
epistaxis, and
diarrhea. Grade 3-5
bevacizumab-related adverse events included
bleeding/
hemorrhage, central nervous system (CNS)
hemorrhage,
hypertension, venous and arterial thromboembolic events, wound-healing complications,
proteinuria, gastrointestinal perforation, and reversible posterior
leukoencephalopathy. The attribution of certain adverse events (e.g., CNS
hemorrhage, wound-healing complications, and thromboembolic events) to either
bevacizumab, underlying disease, or both could not be determined because of the single-arm, noncomparative study design.