The FDA’s Oncologic Drugs Advisory Committee (ODAC) unanimously recommended accelerated approval for bevacizumab (Avastin) for the treatment of glioblastoma multiforme (GBM), an aggressive and nearly uniformly fatal form of brain cancer. The drug’s manufacturer, Genentech, is seeking an indication for bevacizumab as monotherapy for previously treated GBM patients. The panel’s vote of 10-0 for approval was based on results of two phase 2 studies of bevacizumab in GBM.
In one of the studies involving 167 patients with treatment-refractory GBM, bevacizumab monotherapy (10 mg/kg every two weeks) resulted in a partial response rate of 26%, with median a median response duration of 4.2 months. No patients in the study had a complete response. The 6-month progression free-survival rate was 36%, and one-year overall survival was about 38%. Historically, among patients with progressive GBM who receive salvage chemotherapy, on average only about 25% remain alive at one year.
The other study, which involved 56 patients with previously treated high-grade gliomas, produced an objective response rate of 20% and a median duration of response of 3.9 months.
Treatment response in GBM is difficult to assess because the disease disrupts the blood-brain barrier, which often creates significant brain edema. This shows up as increased contrast enhancement on MRI. Bevacizumab reduces the leakiness of blood vessels surrounding the tumor, and consequently improves contrast enhancement. It is unclear, however, to what extent this effect may represent a true anti-tumor response, a concern cited by the FDA panel. There is some evidence that GBM may continue to progress even in the presence of reduced edema. Nonetheless, the advisory panel found the trial results compelling enough to unanimously recommend approval.
The FDA is not obligated to follow advisory committee recommendations, but usually does so. A final agency decision is expected by early May.