After months of speculation the FDA announced that it is recommending withdrawing Roche/Genentech/Chugai's Avastin (bevacizumab) license as a treatment for metastatic breast cancer. In contrast, the European Medicines Agency reaffirmed their approval of the drug in combination with paclitaxel stating that the benefits of Avastin continue to outweigh its risks for metastatic breast cancer patients.

Following a recommendation from the Oncology Drug's Advisory Committee (OCAC) in July 2010 the FDA announced on Thursday the 16th of December that it is recommending withdrawing Roche's Avastin (bevacizumab) license as a treatment for first-line HER2-negative metastatic breast cancer. The FDA concluded that Avastin does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. In contrast, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) reaffirmed approval of the drug on the same day stating that the benefits of Avastin, in combination with paclitaxel, continue to outweigh its risks and that the agent therefore remains a valuable treatment option for patients with metastatic breast cancer. The CHMP has however, decided that Avastin should no longer be used in combination with the Sanofi-Aventis's Taxotere (docetaxel) and has voted against the proposed use of Avastin in combination with Roche's Xeloda (capecitabine) or as a second-line treatment option.

Avastin was granted conditional approval for first-line HER2-negative metastatic breast cancer in the United States in 2008 on the basis of an impressive 52% improvement in progression-free survival in the E2100 study. However, in subsequent Phase III studies (AVADO and RIBBON-1) although demonstrating a statistically significant benefit in progression-free survival, Avastin failed to emulate the magnitude of benefit demonstrated in the original E2100 study. Avastin has also failed to demonstrate an overall survival benefit in metastatic breast cancer however the developers argue that Avastin's Phase III trials were not powered to do so. The agent is associated with several serious side effects which can be life threatening including severe high blood pressure, cardiac toxicity, bleeding and hemorrhage, wound healing complications, perforations throughout the body and the development of a neurological condition called reversible posterior leukoencephalopathy syndrome (RPLS).

The FDA has been careful to stress that their recommendation will not immediately impact breast cancer patients. Indeed Roche have already announced that they will request a public hearing and full review of the FDA's recommendation. This process is likely to take several months and Avastin will remain FDA approved for metastatic breast cancer until conclusion of these proceedings. In the meantime the FDA have advised oncologists to use there medical judgment when making treatment decisions regarding Avastin. Of note, Avastin in combination with paclitaxel is currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines as a first-line treatment option for HER2-negative metastatic breast cancer. In fact this recommendation was reaffirmed by the NCCN in October just three months after ODAC advised that the agent's breast cancer label be rescinded.

The FDA and European Medicines Agency's recent announcements will undoubtedly cause considerable debate amounts the breast cancer oncology community. Decision Resources will be performing primary research in the United States and Europe to ascertain physician opinion of both the FDA and European Medicines Agency's decisions and assess the impact on the U.S. and European breast cancer markets. A Decision Resources Analyst call will be scheduled in January to discuss this topic in detail.

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