On December 10, 2010 the US Food and Drug Administration announced that it was withdrawing its approval for the use of Bevacizumab (Avastin®) for the treatment of metastatic breast cancer. Was this politically motivated? Is this Obamacare run amok? Would women die who otherwise would have lived?
In response to the public’s demand for new cancer drugs, the FDA during the Bush administration devised a faster procedure for bringing new cancer drugs to market. In 2008 it granted expedited but conditional approval for Genentech, the manufacturer of many useful cancer drugs, to sell Avastin for the treatment of advanced metastatic breast cancer. Under Congressionally mandated rules, a condition for expedited approval is the obligation of the FDA to review additional data after a couple of years to confirm or rescind its original approval.
When the Advisory Panel of the FDA reviewed updated efficacy data last year they concluded that the data did not support the use of Avastin for the treatment of advanced breast cancer. In July they voted 12-1 to rescind the approval previously given; in December the final decision was made to uphold the recommendation of the Advisory Panel. The basis for that decision was two later clinical trials which failed to confirm that Avastin, added to best available chemotherapy, improved survival over that seen with chemotherapy alone. In addition the impressive array of side effects of Avastin, mostly related to bleeding and wound healing, made its toxicity a source of concern. A large recent updated analysis confirms a near doubling of treatment-related mortality in patients on Avastin, although the absolute death rate was low.
Is there a story behind the story? Skeptics pointed to the cost of the drug and the push by the Obama administration to rein in health-care costs. Avastin costs $7500/month; the same critics argue that if the drug cost 75 cents/month the approval would have stood. The FDA in response said that statutorily they were not allowed to consider cost in their decision.
However, the recent controversy over the new prostate cancer drug Provenge® and the possibility that Medicare would refuse to pay for it merely because of its cost ($93,000 for a treatment series) stoked the fires of disbelief on the part of breast cancer constituency groups and the right-wing blogosphere. Ironically the rules by which Avastin was approved in the first place were created during the Bush administration; the Obama team had nothing to do with this decision other than appointing the new FDA commissioner.
Will any women die because of the FDA decision? No. All breast cancer patients previously treated with Avastin had far-advanced metastatic disease and most lived only for a few months after treatment was started. It had no curative potential. Since the December decision the FDA has indicated its willingness to work with Genentech to develop additional clinical trials which might shed light on which subset of advanced breast cancer patients could be expected to respond to Avastin. In theory if a subset of patients could be identified (e.g., through the study of gene mutations in the patients’ tumors) who would respond better to this drug than the population as a whole, the drug could be re-approved just for that group.
In the meantime, Avastin is likely to disappear from use in the treatment of metastatic breast cancer – for better or worse.