The recent bevacizumab (Avastin) hearing yielded a result that was not surprising, as the jury, or ODAC [Oncologic Drugs Advisory Committee], members were largely the reviewers who participated in last year's discussion and negative vote. Furthermore, in this era of attempting to have impartial experts by eliminating those with scientific or financial conflicts, it was unfortunate that the panel consisted of so few breast cancer specialists.
Seemingly lost in the emotion of the debate was the simple fact that the addition of bevacizumab to standard therapy reached statistically positive end points in each of the randomized, well-controlled, first-line metastatic breast cancer studies.
The results are complicated by the use of different chemotherapy combinations with Avastin. It is not logical to expect the same outcomes with each regimen. While the "magnitude of benefit" and the lack of an overall survival advantage would certainly have an effect on the prescribing patterns of medical oncologists, those factors do not seem sufficient to withdraw the labeled indication.
The safety and toxicity issues also appear overstated for an agent still approved and widely used in colon, lung, kidney, and brain cancer. The 2 days of hearings were filled with passion and emotion.
It will be interesting to see whether FDA Commissioner Dr. Margaret Hamburg is able to hear through the noise and reach a compromise that will be the best for our patients. For example, the treatment of subsets of women with limited options, such as those with triple-negative breast cancer, could still be part of a more restricted label, as could the treatment of those women already receiving the agent.
Requiring further clinical research, including the investigation of predictive biomarkers, as the sponsor has proposed, is also a reasonable course of action while maintaining the current accelerated approval with paclitaxel. Strategies for oncology drug development, the use of the accelerated approval process, and the design of clinical trials will be greatly affected by this very important decision.
-Howard A. Burris III, M.D.
-William J. Gradishar, M.D.
-Hope S. Rugo, M.D.
Dr. Burris, editor of The Oncology Report, is chief medical officer and director of drug development at the Sarah Cannon Research Institute in Nashville. Dr. Gradishar and Dr. Rugo are associate editors of The Oncology Report. Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology and director of the Maggie Daley Center For Women's Cancer Care at the Robert H. Lurie Comprehensive Cancer Center and Northwestern University Feinberg School of Medicine in Chicago. Dr. Rugo is clinical professor of medicine and director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco.