Rethinking Breast Cancer and Bevacizumab

Published - Written by Rena Xu

The Food and Drug Administration (FDA) recently revoked its approval of the agent bevacizumab (also known as Avastin), a monoclonal antibody against vascular endothelial growth factor A, for treating metastatic breast cancer. Did they act too fast?

According to Von Minckwitz et al., bevacizumab, when added to neoadjuvant chemotherapy, may offer considerable benefits for patients with certain types of early breast cancer.

In this week’s NEJM, the authors report the findings of a clinical trial that enrolled almost 2,000 patients with early-stage breast cancer. The patients were randomly assigned to receive either the chemotherapy agent docetaxel alone or with concurrent bevacizumab. The investigators then looked at the pathological complete response, defined as the absence of residual tumor in the breast and surrounding lymph nodes.

They found that overall, the pathological complete response was improved with the addition of bevacizumab (18.4%, as compared to 14.9% with docetaxel alone; P=0.04). The improvement was particularly striking for the subgroup of patients with triple-negative tumors – tumors that lack receptors for estrogen and progesterone and that don’t overexpress HER2. Among these patients, the pathologic complete response with the addition of bevacizumab was 39.3%, as compared to 27.9% with neoadjuvant chemotherapy alone (P=0.003).

This finding may hold important treatment implications; as the authors note, a better pathological complete response has been shown to correlate with a lower rate of relapse and death for HER2-negative breast cancer. However, the follow-up time for this study was not long enough to determine whether pathologic complete response in fact translated into an improvement in survival.

Drs. Alberto Montero and Charles Vogel of the University of Miami Department of Hematology/Oncology note in an accompanying editorial, “The ongoing controversy surrounding bevacizumab therapy for breast cancer goes beyond the science of tumor angiogenesis and involves broader questions about the use of surrogate end points in clinical trials, as well as economic arguments over the ever-increasing cost of new medicines for the treatment of cancer.”

Indeed, the FDA had decided to revoke its approval of bevacizumab as a treatment option for metastatic breast cancer on the basis of an unclear survival benefit. These new findings suggest, at the very least, that there is still room for debate – not only about the suitability of bevacizumab specifically as a treatment for breast cancer, but also more broadly about what end points should guide clinical practice and drug use regulations.

What has been your experience with using bevacizumab to treat breast cancer? How much weight do you place on surrogate endpoints like progression-free survival when designing a treatment regimen?