Bevacizumab in the treatment of metastatic breast cancer

Abstract

Vascular endothelial growth factor (VEGF) is the major positive regulator of its receptor (VEGFR2) which mediates angiogenesis physiologically as well as in malignant diseases. Many tumors secrete high levels of VEGF leading to a high number of newly built peritumoral blood vessels, which has been identified as an independent prognostic indicator for tumor recurrence and survival in breast cancer. Therefore, inhibiting angiogenesis may be an effective antitumor treatment in breast cancer as well as in other malignant diseases. Bevacizumab is a potent humanized monoclonal antibody to VEGF, which has shown regression of solid tumors in clinical and preclinical trials alone or in combination with cytotoxic treatment. Phase I/II trials showed significant antitumor effects of bevacizumab against several solid tumors including breast cancer. Toxicities were moderate including hypertension, bleeding and proteinuria. A first phase III trial in pretreated metastatic breast cancer (MBC) patients who had received prior chemotherapy for metastatic disease showed better response rates but no benefit from the addition of bevacizumab to capecitabine with regard to progression- free and overall survival. However, in another phase III trial in patients with MBC without prior systemic treatment for metastases, bevacizumab improved progression-free survival in combination with weekly paclitaxel in comparison to paclitaxel alone. Bevacizumab in combination with paclitaxel seems to be a highly effective first-line treatment for MBC patients. Further trials will have to show its effects in other indications. © 2007 S. Karger GmbH.