FDA Yanks Approval for Avastin in Metastatic Breast Cancer

Food and Drug Administration (FDA) Commissioner Margaret Hamburg Friday upheld the Agency's decision to remove its seal of approval on the drug Avastin (bevacizumab) for treating women with breast cancer that has spread beyond the breast.  In practice, this will have little effect on the prescribing of the drug to treat breast cancer, since the indication remains in the compendium of the National Comprehensive Cancer Network (NCCN). Even the stodgy federal insurance program Medicare will continue to cover the drug.

Ms. Hamburg cited the potentially fatal risk of the drug (for instance, high blood pressure, bleeding and clotting emergencies) do not outweigh the benefit of the drug, which, when first approved, was thought to be an approximate six month delay in disease progression.  Additional clinical trials, however, could not replicate the six month advantage, showing only a one- to two-month progression free survival advantage.  It is important to note that Avastin has never shown an actual overall survival (that is, a delay in death) when used to treat breast cancer.  So Ms. Hamburg is possibly right about the limited (if any) benefit.

Where she is wrong ... well, not actually wrong, but clueless . . . is with regard to the risky side effects.  Margaret:  get real!  We're talking about women with metastatic breast cancer. Women who are going to die from their disease.  What risk is greater for them than forgoing treatment?

The interesting - exciting, even - development that has been overlooked in the debate between Avastin's manufacturer, Genentech, and the FDA, is Avastin's positive impact in subsets of women with advanced breast cancer. In particular, the same studies that showed equivocal benefit in breast cancer patients overall actually showed great promise in the highest risk group: women with triple-negative breast cancer (i.e., cancer that is impervious to her-2 antibody therapy as well as to hormone treatments).

In the burgeoning world of targeted therapy, where Avastin is perhaps a prehistoric drug, new opportunity rests in testing tumors that produce high levels of vascular endothelial growth factor (VEGF).  Pre-clinical studies in cervical cancer, for instance have shown significant anti-cancer activity in tumors that produce high VEGF levels, as compared with cervical cancer tissue that produces little or no VEGF.

Which is to say that, even if the FDA refuses to endorse Avastin today, the agency may very well be required to reverse its decision in the near future, at least for the targeted tumor types for which Avastin will prove to be life-extending.