FDA Approves Bevacizumab for Metastatic Breast Cancer

NEW YORK -- Bevacizumab (Avastin) is now approved as a first-line option for patients with metastatic, HER2-negative breast cancer. The approval is based on a phase 3 study (E2100) that found bevacizumab in combination with paclitaxel reduced the risk of disease progression or death by 52 percent compared with those treated with paclitaxel alone. Adding bevacizumab to paclitaxel also doubled progression-free survival (PFS) [hazard ratio (HR) = 0.48; P < .0001].Bevacizumab was approved in advanced breast cancer under the US Food and Drug Administration's accelerated approval program, which allows the FDA to approve products for cancer or other life-threatening diseases based on initial positive clinical data. Genentech, Inc. the maker of bevacizumab has shared with the FDA a summary of the results from a second positive phase 3 trial (AVADO), and is expecting results from a third phase 3 trial (RIBBON I) in first-line metastatic breast cancer in late 2008. A full review of both the AVADO and RIBBON I data by the FDA will be required for the accelerated approval to be converted into a full approval."There is no cure for metastatic breast cancer, so it is important to control the disease as early and for as long as possible," said Kathy Miller, MD, Associate Professor of Medical Oncology, Indiana University School of Medicine, Indianapolis, and lead investigator on the E2100 trial. "Now with [bevacizumab] plus paclitaxel, we can increase the time a woman's cancer is kept under control, and offer a biologic option to women who previously were limited to chemotherapies alone."E2100 was a multicenter, randomized, controlled clinical trial (N = 722) of patients with previously untreated, locally recurrent or metastatic breast cancer. Patients received weekly treatment with paclitaxel every 3 out of 4 weeks, with or without bevacizumab. Based on an independent, blinded review of patient scans, median PFS was longer in patients treated with bevacizumab plus paclitaxel compared with paclitaxel alone (11.3 mo vs 5.8 mo). The independent review showed a similar magnitude of benefit relative to the initial results presented by the Eastern Cooperative Oncology Group (ECOG) at the American Society of Clinical Oncology annual meeting in 2005. Overall survival, a secondary endpoint, was 1.7 months longer (P = .14) in the bevacizumab-containing arm (HR = 0.87), supporting the primary endpoint of PFS.These safety findings were generally consistent with previous trials of bevacizumab plus chemotherapy, and no new safety signals related to bevacizumab were observed. Grade 3/4 adverse events that occurred more often in the bevacizumab arm included neuropathy (due to longer time on paclitaxel treatment), hypertension, arterial thromboembolic events, and proteinuria.Source: Genentech, Inc.