Patients with metastatic breast cancer using bevacizumab as a treatment: is there still a role for it?

Over the last few decades, the angiogenesis mechanism has increasingly been studied and implicated in cancer pathophysiology. At present, it is known that angiogenesis plays a relevant role in tumor growth, and more importantly many new molecules exists can potentially interfere with this process. Bevacizumab, a humanized monoclonal antibody targeting the vascular endothelial growth factor A (VEGF-A) now commonly used in the treatment of colorectal, renal cell, and brain cancer, is the first anti-angiogenesis drug delivered in combination with chemotherapy that has consistently shown clinical efficacy in the treatment of breast cancer. Since the ECOG 2100 trial has shown that bevacizumab added to paclitaxel as a first-line treatment for advanced breast cancer nearly doubled the time to progression and tumor response rate, its approval was granted almost worldwide. However, other phase III trials revealed a smaller absolute improvement in progression-free survival (PFS) and response rates, and no trials yet have demonstrated survival enhancement which led to a great controversy and debate over the use of bevacizumab. The discrepancy between PFS and overall survival also raises the question of whether or not bevacizumab has been applied sub-optimally in some of the studies, if a predictive biomarker(s) exists to select the group of patients whom would receive the greatest benefit and what is the appropriate clinical end-point for approval and funding of new targeted agents. In this article we will review the bevacizumab mechanism of action and the clinical trials that assessed its benefit in the treatment of metastatic breast cancer (MBC).