Bevacizumab for recurrent glioblastoma multiforme: a meta-analysis.

The FDA's approval of bevacizumab for recurrent glioblastoma on May 9, 2009, was based on the significant response rate and clinical benefits seen from randomized phase II studies. Large-scale phase III data are unavailable. In an effort to determine benchmark efficacy parameters for bevacizumab and analyze its dose--response effect, the authors performed a meta-analysis of 15 studies published from 2005 to 2009, involving 548 patients with a median age of 53 years (range, 5-74 years), that used bevacizumab to treat recurrent glioblastoma. Median overall survival was 9.3 months (95% CI, 7.9-10.6 months). The respective 6-month progression-free and 6-month overall survival rates were 45% (95% CI, 34%-57%) and 76% (95% CI, 69%-84%), respectively. Median time to tumor progression was 6.1 months (95% CI, 4.2-8.1 months). The response analysis yielded a 6% complete response (95% CI, 2%-9%), 49% partial response (95% CI, 37%-61%), and 29% stable disease (95% CI, 20%-38%). No difference was seen in bevacizumab dose--response benefit between 5 mg/kg and 10 to 15 mg/kg. The efficacy benchmarks from this meta-analysis did not differ from those of the recently published randomized phase II studies. The lack of a dose--response effect would require confirmation in a prospectively conducted clinical trial.