Yesterday the Food and Drug Administration moved to revoke its regulatory approval of Avastin for metastatic breast cancer. Withdrawing a cancer treatment is almost never done, and though the decision was expected, that does not make it any less reprehensible.
The FDA said in a statement that it is removing Avastin's breast cancer indication because the biologic does not provide "a sufficient benefit in slowing disease progression to outweigh the significant risk to patients." Ponder that "sufficient." The agency is substituting its own judgments about clinical meaningfulness for those of practicing oncologists and terminally ill cancer patients.
The risks of Avastin are real, but manageable. Clinical trials do not show that the drug extends life overall in the aggregate, but they have shown that it allows women to live longer without their disease getting worse. Avastin improves progression-free survival by about four months on average. Different patients respond differently, and the drug is far more effective in some than in others, for reasons that researchers still do not understand. There aren't any perfect therapeutic options in end-stage oncology, and Avastin ought to have remained one of them.
Looking at the same data, the European Medicines Agency—the FDA's counterpart in the European Union—decided on Thursday that it would continue to approve Avastin for breast cancer in combination with chemotherapy. In October, the U.S. National Comprehensive Cancer Network—a consortium of 21 leading cancer centers that issues evidence-based medical guidelines—reaffirmed its position that Avastin is valuable in some cases.
But such finely graded distinctions are not part of the FDA's bureaucratic culture. The FDA provisionally (and reluctantly) approved Avastin for breast cancer in 2008 under an accelerated process for serious diseases. But the cancer drugs division believes that such flexibility is too friendly to industry and took extraordinary measures to rig the review process against Avastin's maker, Genentech, as we reported on August 18 in "The Avastin Mugging."
Genentech is contesting the ruling through a formal FDA appeals mechanism, and Avastin will remain available on an "off label" basis, because it is still approved for other cancers such as those of the lung, kidney and brain. However, private insurers are generally reluctant to reimburse for therapies that are not FDA-approved, and Medicare, which is the dominant payer in oncology, never does.
One depressing implication is what the decision says about health-care financing as government entitlements expand. Avastin is a political target because of its high cost—a typical course runs as high as $88,000—and after ObamaCare all medical questions are inevitably political questions too. In September, the FDA and Medicare proposed a "parallel review" process that will allow the two agencies to coordinate market and reimbursement approval. Medicare is also increasingly opening "national coverage determination" reviews that allow a government board to decide if a therapy is "reasonable and necessary."
Another danger is to the future of medical innovation. Cancer treatment advances incrementally. Every year doctors are better able to pair medicines with the biomarkers pointing to the individuals who are most likely to respond and learn more about tumor angiogenesis, which is the process of cancer growth that Avastin helps to choke off. The FDA's assault will make it harder to conduct and enroll patients in further clinical studies, to say nothing of its message about the regulatory risk for drugs still in development.
The greatest tragedy will fall on the women who are suffering from an incurable disease and whose caregivers are trying to improve their quality of life in the months they have left. The FDA is taking away one of their only options.