WASHINGTON -- The FDA has announced that bevacizumab (Avastin) is no longer approved for the treatment of breast cancer. The Genentech drug retains its indications for colon, lung, kidney, and brain cancer and will remain on the market.
The FDA's Oncologic Drugs Advisory Committee had voted unanimously in June that bevacizumab should no longer be approved to treat metastatic HER2-negative breast cancer. That meeting had been convened at Genentech's request to appeal the FDA's earlier decision to remove bevacizumab's breast cancer indication.
"This was a difficult decision," FDA Commissioner Margaret Hamburg, MD, said on Friday morning. "I feel deeply for these women suffering from breast cancer . . . who are seeking therapies that may work for them." Hamburg told reporters during a call following the announcement.
"However," she said, "when the totality of the evidence is examined, there is really not a clear demonstration that the benefits of this drug outweigh the risks."
Hamburg mentioned several times that although bevacizumab will no longer be FDA approved for breast cancer, doctors may very well continue to prescribe it off-label for that condition.
However, at the FDA advisory committee meeting last summer, a handful of breast cancer patients known as "super-responders" -- women who seem to have responded remarkably well to bevacizumab - begged for continued approval of the drug, noting that their insurance companies are unlikely to pay for the $8,000-a-month drug if the FDA strips away the breast cancer indication.
After that meeting, Medicare said it would continue to pay for bevacizumab to treat metastatic breast cancer even if the FDA decides to remove that indication from the drug.
Genentech received accelerated approval for the indication in 2008 after a study showed that patients taking bevacizumab had an average 5.5 months more progression-free survival than those treated with paclitaxel alone (11.3 months versus 5.8 months).
As a condition of the fast-track approval, Genentech was required to conduct more clinical trials to prove efficacy and safety.
"Additional studies failed to confirm the drug's promise," Hamburg said.
In the follow-on studies, the impressive 5.5 months of progression-free survival with bevacizumab seen in the earlier trial nearly disappeared (to just 0.8 months difference), and no new benefits were observed (such as improved quality of life or survival).
What was apparent, however, were the side effects, Hamburg saidin her 69-page decision. Those included severe hypertension, hemorrhage, MI, heart failure, and perforations in the nose, stomach, and intestines.
"After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks," Hamburg said. "Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life."
Genentech said it was disappointed in Hamburg's decision.
"We remain committed to the many women with this incurable disease and will continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment," Genentech spokeswoman Charlotte Arnold said in a statement.
Arnold said the company will start a new phase III study of bevacizumab in combination with paclitaxel in previously untreated metastatic breast cancer. The study will use specific biomarkers to better pinpoint which women may be most likely to benefit from bevacizumab.
Hamburg said she encourages Genentech to consider additional studies.