NBCC made the case in 2008 that accelerated approval for bevacizumab (Avastin®) was lowering the bar on drug approval. There was no evidence the drug extended the lives of breast cancer patients, and some evidence it increased the risk of harm. The FDA granted accelerated approval on the basis of a clinical trial showing an increase in progression-free survival but no increase in overall survival, with the understanding that tumor shrinkage was a potential surrogate for a more meaningful outcome. We now know this isn’t the case. We also knew then that Avastin® increased the risk of serious side effects, such as hypertension, increased infections, low white blood cell count, proteinuria, and gastrointestinal perforations.

The follow-up studies presented to the FDA this week confirmed that the drug does not work for breast cancer patients while at the same time it increases the risk for serious side effects. The studies presented to the FDA demonstrated a higher incidence of side effects requiring medical intervention, hospitalization or resulting in death for the groups receiving Avastin® in combination with chemotherapy vs. those receiving chemotherapy alone. The data show that Avastin® should no longer be used in the treatment of breast cancer. We also believe there is no reason to continue to subject women to this drug in clinical trials.

The goal of drug approval is to make available drugs that save lives, that significantly extend survival while maintaining a good quality of life. The accelerated approval process was launched in 1992 to allow earlier approval of drugs to treat serious diseases, and that fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker or substitute measurement that represents a clinically meaningful outcome, such as survival or symptom improvement. Approval of a drug based on such endpoints is given on the condition that post-marketing clinical trials verify the anticipated clinical benefit.

Accelerated approval makes sense if in fact the benefits far outweigh the risks of the conditionally approved drug if there was a strong basis to conditionally approve the drug, to begin with, and if the overall benefit to breast cancer care and research is clear. None of these criteria were present in any aspect of the Avastin® accelerated approval story. The accelerated approval process should not be used to release drugs to the public when there is evidence of harm and minimal evidence of benefit and then wait to see what happens. We need to have good data from clinical trials to indicate a benefit and safety before approval of any kind. At the moment, Avastin® is being given off-label to women with breast cancer in the adjuvant setting. Avastin® is being tested for women with breast cancer in early and late stages in more than 93 trials. New patients are being recruited into another 87 new trials testing Avastin® in breast cancer. Too many women are being subjected to a drug that we know does not extend their lives and does increase the risk of serious side effects.