Despite a growing body of evidence with the use of these agents, efficacy and safety results do not tell the complete story with bevacizumab as combination therapy. Perhaps no other oncologic drug in recent memory has caused as much controversy as bevacizumab. In July 2010, the Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) voted 12-1 to recommend withdrawal of the conditional approval of bevacizumab as front-line therapy for HER2 negative mBC based on their concerns of the potential serious adverse events with this agent, the lack of confirmation of the magnitude of benefit seen in the E2100 trial (comparing paclitaxel with and without bevacizumab10
) in the RIBBON-1 trial, as well as the AVADO trial, another seminal trial examining docetaxel with or without bevacizumab11
and the lack of improvement in OS in all those trials. On December 15, 2010, the FDA’s Center for Drug Evaluation and Research recommended to initiate the process of withdrawal of the approval of the breast cancer indication for bevacizumab.27
Subsequently, Europe’s regulatory body, the European Medicine Agency, released a statement that bevacizumab would remain as an option for metastatic breast cancer, but only when used in combination with paclitaxel.28
On June 27th–28th, 2011, the FDA conducted a hearing with the Center for Drug Evaluation and Research and the manufacturer of bevacizumab, Genentech, which further explored the approval of bevacizumab for treatment of metastatic breast cancer.29
Following this meeting the Centers for Medicare & Medicaid Services made a public statement that they will continue to pay for bevacizumab when it’s used to treat metastatic breast cancer, even if the FDA decides to remove that indication from the drug.30
Also the National Comprehensive Cancer Network (NCCN), has voted overwhelmingly in favor of maintaining its recommendation that bevacizumab should continue to be available as an option to treat mBC.31
A final ruling from Dr. Margaret Hamburg, commissioner of the FDA, was still pending at the time of submission of this manuscript. Although bevacizumab is in no danger of removal from the market because of its current indications in other tumor types, the removal of the breast cancer indication from the labeling of bevacizumab would likely result in decreased ability of researchers and providers to use this medication in mBC.
It is also impossible to have a meaningful discussion regarding the use of bevacizumab in breast cancer without mentioning the concerns over cost of therapy. A study from Switzerland utilized the data from the avf2119, E2100, and AVADO studies to determine the cost-effectiveness of the addition of bevacizumab therapy in MBC.32
The conclusion of this study, conducted under the constraints of the Swiss health system, was that addition of bevacizumab to weekly paclitaxel was estimated to cost 40,369 euros (approximately $58,000 US dollars) for the gain of 0.22 quality adjusted life years, equaling an incremental cost-effectiveness ratio of 189,427 euros ($272,812 USD) per QALY gained. Of course, the improvement in survival needed to justify the use of a particular agent is subjective, but the authors point out that bevacizumab is expensive compared to common willingness-to-pay thresholds.