Bevacizumab plus docetaxel meets primary endpoint for advanced breast cancer

Genentech currently awaiting FDA decision on bevacizumab in combination with paclitaxel therapy.

Progression-free survival improved with combination bevacizumab and docetaxel therapy in previously untreated patients with recurrent or metastatic HER2-negative breast cancer, according to a press release announcing the phase-3 AVADO results on Tuesday.

The announcement came just weeks before the FDA is scheduled to make a decision on Genentech Inc.’s supplemental Biologics License Application for the use of bevacizumab (Avastin, Genentech Inc.) in combination with paclitaxel therapy, according to the press release. The FDA is expected to have a decision by February 23, 2008.

“The [AVADO] trial demonstrated [bevacizumab’s] potential with a different chemotherapy in this disease,” Hal Barron, MD, senior vice president, development and chief medical officer at Genentech Inc., said in a press release. “The AVADO data are not included in the supplemental Biologics License Application currently under review by the FDA. However, we have shared the AVADO data with the FDA to assist the agency in assessing the risk and benefit of [bevacizumab] in this patient population.”

Methodology

In the international, multi-center, randomized and placebo-controlled trial, 736 patients were randomly assigned to 15mg/kg or 7.5 mg/kg of bevacizumab or placebo every three weeks in combination with docetaxel at 100 mg/m² every three weeks for up to nine cycles, according to the press release.

Patients who discontinued docetaxel after nine cycles or as a result of toxicity were to continue bevacizumab or placebo until their disease progressed.

Genentech Inc. is withholding additional data on the AVADO trial for presentation at the American Society of Clinical Oncology Annual Meeting in June.

High hopes

In December, the FDA advisory panel voted 5 to 4 to pass on the drug’s approval due to a lack of sufficient data from the E2100 trial. (“Advisory panel votes down bevacizumab for metastatic breast cancer,” January 2008)

The safety and efficacy of paclitaxel plus bevacizumab were examined in patients with untreated metastatic breast cancer enrolled in E2100. Though a 5.5-month increase in median progression-free survival was reported in patients who received bevacizumab, an increased rate of grade-3 to -5 adverse events was also reported in the group, aiding the FDA’s decision to vote down the drug.

After reviewing E2100 data, panel members agreed that progression-free survival, in first-line metastatic breast cancer, is a more meaningful endpoint than overall survival, which appears to be good news for Genentech. Despite the FDA’s previous decision, the company remains hopeful that the safety and efficacy of bevacizumab in this setting are substantiated by the results of the AVADO trial. – by Stacey L. Adams