Bevacizumab (Avastin?, Genentech/Roche) in combination with paclitaxel remains a treatment option for women with breast cancer, but not with other combinations. Earlier today the European Medicines Agency (EMA) confirmed that the benefits of bevacizumab in combination with paclitaxel outweigh its risks and that this combination remains a valuable treatment option for patients suffering from metastatic breast cancer.
The decision by the European regulators contradicts the today?s announcement by the U.S. Food and Drug Administration to start a procedure to remove the breast cancer indication from the bevacizumab label.
In addition the assessment that combination of bevacizumab in combination with paclitaxel remains a valuable treatment option for patients suffering from metastatic breast cancer, the European Agency?s Committee for Medicinal Products for Human Use (CHMP) also concluded that the balance of benefits and risks of bevacizumab in combination with docetaxel is negative and that this combination should no longer be used in the treatment of breast cancer. Patients who are currently being treated with this combination should discuss their ongoing treatment with their doctor.
Bevacizumab is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor). VEGF is the key driver of tumor angiogenesis ? a fundamental process required for a tumor to grow and to spread (metastasise) to other parts of the body. Bevacizumab?s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Bevacizumab helps to control tumor growth and extend survival with only a limited impact on the side effects of chemotherapy. It’s used in combination with other anticancer treatments to treat cancers of the colon, rectum, lung, kidney or breast. The CHMP?s review was restricted to the use of bevacizumab in breast cancer and does not affect its use in the other indications.
The CHMP carried out the review of bevacizumab in breast cancer under provision listed in Article 20 of Regulation (EC) 726/2004. The review was initiated because new data from a study of the use of bevacizumab in the treatment of metastatic breast cancer suggested that bevacizumab in combination with docetaxel may have a negative impact on the overall survival. The study was submitted to the Agency to support an application to extend the breast cancer indication for bevacizumab to include combination therapy with capecitabine.
Combination therapy of bevacizumab and docetaxel for metastatic breast cancer was approved in September 2009 on the basis of data that showed a small but significant increase in progression-free survival (how long the patients lived without their disease getting worse), and no detrimental effect on overall survival.
The new data submitted to the Agency add uncertainty about the effect on overall survival and a detrimental effect on overall survival cannot be excluded. The new data also question the size of the effect on progression-free survival, which appears to be smaller than previously observed. Because the increase of progression-free survival remains very small, the CHMP concluded that the benefits of bevacizumab in combination with docetaxel no longer outweigh its risks.
For bevacizumab in combination with capecitabine, the Committee found that although the data showed a modest increase in progression-free survival, no clinically relevant effects were observed on other endpoints such as overall survival or health-related quality of life. The relatively modest benefits were considered not to outweigh the high toxicity of the combination of bevacizumab and capecitabine, given that the new indication was aimed at patients for whom a relatively mild treatment would be appropriate. Therefore the Committee concluded that the new indication should not be approved.
For bevacizumab in combination with paclitaxel, the Committee concluded that the benefits continue to outweigh the risks, because the available data have convincingly shown to prolong progression-free survival of breast cancer patients without a negative effect on the overall survival. The Committee therefore recommended that for the treatment of breast cancer bevacizumab should only be used in combination with paclitaxel.
The Committee?s recommendations have been sent to the European Commission for the adoption of a decision.