BEVACIZUMAB APPROVED FOR RECURRENT GLIOBLASTOM

May 6, 2009 — The US Food and Drug Administration (FDA) has granted accelerated approval for bevacizumab (Avastin, Genentech) for use in patients with glioblastoma that has progressed despite previous therapy. This is the first drug to be approved for this indication in more than a decade.

This is an area of "unmet medical need," said Henry Friedman, MD, deputy director of the Preston Robert Tisch Brain Tumor Center at Duke University in Durham, North Carolina. There is currently no standard of care for such patients, and no option that produces a true meaningful benefit, he told Medscape Oncology.

Bevacizumab has unequivocally displayed benefit in these patients, he said. "It gives us a new weapon and gives patients a chance for longer survival and a chance of improvement in their quality of life," he said.

The approval comes just weeks after a unanimous vote by the Oncological Drugs Advisory Committee (ODAC), with all 10 members recommending accelerated approval, as reported by Medscape Oncology . This is despite the fact that the clinical data for this indication come from clinical trials with no comparator — the benefit seen was in comparison to historic controls.

One of the trials (known as AVF3708g, or BRAIN) involved 167 patients with glioblastoma who had progressed on radiation and temozolomide (Temodar, Schering) and who then received bevacizumab either alone or in combination with irinotecan. According to an FDA analysis of the study, tumor responses were observed in 22 of 85 patients (26%) treated with bevacizumab alone, and the median duration of response was 4.2 months.

In another trial (NCI 06-C-0064E), 56 patients with recurrent glioblastoma were treated with bevacizumab alone. Responses were observed in 11 patients (20%), and the median duration of response was 3.9 months.

There are no data so far from randomized trials for overall survival.

"There was some concern that the FDA was going to demand a comparator trial, but the totality of the data was so good in terms of response rate, progression-free survival, overall survival, the decrease in corticosteroid use, the maintenance of neurocognitive function, and the overall clinical improvement in the patients, plus the lack of any other options, proved to be compelling," Dr. Friedman said. He was principal investigator for this trial, and he acted as an advisor to the manufacturer for the design and analysis of the trial. Dr. Friedman was also on the ODAC committee.

"The benefit to the patient was real and unchallengeable," he said.

Bevacizumab has already been used in this indication in the United States, but because this is an off-label use, there were problems with third-party coverage in some instances. These problems should now disappear, he added.

Further trials are in progress, both single-group and randomized trials, looking at bevacizumab in combination with surgery, radiation, and temozolomide in patients with newly diagnosed glioblastoma.

Bevacizumab, a monoclonal inhibitor of vascular endothelial growth factor, is already approved in the United States for use in colorectal, lung, and breast cancer.