After 5 months of deliberation, FDA Commissioner Margaret Hamburg, the final arbiter in the Avastin hearings, decided to revoke approval of the drug in patients with metastatic breast cancer. At first blush, this event would seem to end the story. But not so fast! Even though Avastin cannot be marketed for this indication, it still can be prescribed “off label” as oncologists have done in the past for many agents. And, this ruling doesn’t affect its use for other indications including colon, lung, kidney and brain cancers. Medicare will continue to reimburse for Avastin use in breast cancer patients. But response of private insurers has been variable so far. All of the above has a familiar ring to it. The situation is almost exactly the same as it was when hearings ended in June.
We have extensively covered these hearings and the articles on which this decision is based in prior blogs and radio broadcasts. The data clearly documented that no complete remissions were achieved and, therefore, there were no cures. In the Wall Street Journal report (WSJ; Saturday/Sunday, November 19-20, 2011, pp. B1-B2), Rep. Sue Myrick (R., N.C.) is quoted as saying: “When a drug can help save patients’ lives, they should be able to do that affordably.” Her point was that this decision may result in denial of coverage. But stating that Avastin saves the lives of breast cancer patients implies a cure, giving thousands of women false hope. Yes, I’ve personally treated many breast cancer patients with Avastin. Some have lived months longer than they would have without it. Rarely years. But none have been cured.
Coverage of the FDA’s decision has been rapid and extensive. This morning’s AMA Morning Rounds provides an excellent compendium of what’s been published or aired so far. I found the last 2 cited sources especially interesting, providing a “point-counterpoint” perspective:
“WSJournal critical of FDA move. The Wall Street Journal (11/19, Subscription Publication) argued that the FDA’s requiring credible, objective evidence is a subjective standard and criticized the government for interfering with patients’ choices. The Journal argued that the FDA and medical journals dislike the accelerated approval process for medicines and that its decision isn’t based on Avastin’s side effects but an effort to convey a message that the agency is in charge of pharmaceutical development. The Journal asserted that the FDA was ignoring the real world and should have allowed Avastin to remain on the market while more was learned about it.”
“FDA decision applauded. On a blog in Forbes (11/19), Matthew Harper wrote, ‘the FDA decision is the right one, and, more than that, it’s actually good for the drug industry.’ According to Harper, the opposite decision ‘would have made scientists who work at the regulator or who advise it on expert advisory committees more reluctant to give accelerated approvals at all.’ Furthermore, ‘we’re not going to beat cancer by lowering the bar.’ Harper notes, ‘that Avastin costs $80,000 for the average breast cancer patient, and Roche pockets the money whether it works or not,’ adding, ‘we can’t afford to fight cancer with weapons that don’t both shrink tumors and prolong patients’ lives.”
Recognizing these divergent opinions are being read and heard by our patients and their families and friends, how do we advise them about Avastin’s appropriate role in breast cancer, if there are any? Thoughts of two respected breast cancer researchers, Joyce A. O’Shaughnessy, M.D. and Hope S. Rugo, M.D., are reasonable. They are stated in the OncLive issue; Vol 12 No 9, 9.11, pg 18: “Insights on Avastin: Patient Selection Is Key.” This selection process should obviously identify both those patients most likely to benefit and those most likely to suffer adverse reactions:
- At this point in time, we haven’t identified biomarker(s) predictive for response. Preliminary data suggesting that levels of VEGF-A may identify a subset of patients potentially responsive to Avastin is apparently being investigated. Until such a marker is identified, it is reasonable to recommend weekly, low dose Taxol + Avastin 10 mg/kg IV q2wks. for aggressive tumors, e.g., triple negative disease. We have the option of hormonal therapy in addition to chemotherapy for ER+/PgR+ patients, and Heceptin and chemotherapy for HER-2+ patients.
- By avoiding Avastin in patients at increased risk for complications (recent surgery, planned surgery in the near future, diverticulitis, active body wounds, or uncontrolled hypertension at baseline), safety of administration can be improved.
Don’t blink. We probably haven’t heard the last of this evolving story. But that’s as it should be. Nothing in medicine is exempt from testing to see if it can be done better.