Reappraisal of the role of bevacizumab in the therapeutic strategy in advanced renal cell carcinoma.

Increased understanding of the molecular pathophysiology of metastatic renal cell carcinoma (mRCC) has led to development of antiangiogenic therapies in the past 5 years that significantly improved the prognosis. Vascular endothelial growth factor (VEGF) is a major growth factor in tumor angiogenesis and is implicated in tumor progression of several types of cancer, including mRCC. Use of 2 distinct approaches resulted in clinical efficacy in blocking the VEGF pathway: small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, axitinib, pazopanib) and the humanized anti-VEGF monoclonal antibody bevacizumab that binds circulating VEGF and prevents activation of the VEGF receptor. In the 2 large phase III trials AVOREN and CALGB 90206, bevacizumab combined with interferon alfa demonstrated its efficacy as a first-line therapy in terms of progression-free survival. Nevertheless, in the era of targeted therapies, other studies are still needed to better obtain the maximal clinical benefit of bevacizumab. The aim of this overview is to report the current role of bevacizumab in the treatment of metastatic kidney cancer and to highlight possible combinations or sequential strategies that involve other targeted agents.