BEVACIZUMAB FOR GLIOBLASTOMA

Bevacizumab in Glioblastoma Approval Recommended

April 2, 2009 — Bevacizumab (Avastin, Genentech/Roche) has been recommended for accelerated approval for use in patients with previously treated glioblastoma by the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC). The FDA is expected to make a decision about the approval by May 5.

The vote for recommending approval was unanimous, with all 10 members agreeing, James Vrendenberg, MD, professor of medicine at Duke University, in Durham, North Carolina, told Medscape Oncology. He expects that the FDA will grant this approval. Bevacizumab is already being used by many clinicians in the United States for previously treated glioblastoma, because this is a setting of urgent medical need in which there are no other beneficial therapies, he said.

This will be an additional indication for the product. Bevacizumab, a monoclonal antibody inhibitor of vascular endothelial growth factor (VEGF), is already approved for use in colorectal, lung, and breast cancer

Dr. Vrendenberg was present at the ODAC meeting as 1 of the investigators of the clinical trial that was being discussed and as a consultant for the manufacturers.

The clinical data presented at the meeting came from a phase 2 trial that had no comparator group, but the results were significantly better than have been seen with historic controls, and the response rate was 4 times higher "than has ever been seen," Dr. Vrendenberg noted. Previous studies have investigated irinotecan, lomustine, etoposide, and other drugs, he said. The response rate was defined as a decrease in tumor size by at least 50% on 2 consecutive independent assessments at least 4 weeks apart.

"All the data went in the same direction of benefit," he continued. The results for 6-month progression-free survival, overall survival, and discontinuation of steroids were all significantly better than historic controls, so there was a "clear story of benefit," he added.

The study, known as BRAIN, was conducted in 167 patients with previously treated glioblastoma and, "when it was being designed, we felt it was immoral to have a comparator arm that would be ineffective," Dr. Vrendenberg said. That group would have been irinotecan alone, but there had already been several studies suggesting that bevacizumab is effective in this patient population. Hence, the study offered patients either bevacizumab alone (n = 85 patients) or bevacizumab in combination with irinotecan.

These patients had previously been treated with radiation and temozolomide (Temodar, Schering-Plough), which is the established standard therapy for newly diagnosed glioblastoma. This is the setting in which 2 new trials are exploring whether the addition of bevacizumab can improve outcomes. Both are phase 3 trials, with results expected in about 2014.

"Bevacizumab is a major step for the brain tumor community, and takes advantage of glioma biology to treat it more effectively," Dr. Vrendenberg commented.

Gliomas are very dependent on VEGF, he explained. "So this is the 1 tumor — in addition to renal cell carcinoma — in which you would predict that VEGF inhibitors would work well and other treatments would not work well. And that's what we have found; it has just taken a long time to test it."

"I also think this is just the beginning," he added. "There are some very exciting clinical trials and there is hope for better survival for brain tumor patients."