Vascular Endothelial Growth Factor Pathway—Targeted Therapy as Initial Systemic Treatment of Patients with Renal Cancer

Advanced renal cancer is known to be largely refractory to traditional DNA- and DNA repair—targeted chemotherapy. Until recently, immunotherapy had been the mainstay for the treatment; however, it is effective in only a small proportion of patients. Advances in the understanding of the association between the von Hippel—Lindau pathway and angiogenesis and their role in the development of renal cancer has led to the development of highly effective vascular endothelial growth factor (VEGF) pathway—targeted inhibitors. Several such novel agents have demonstrated increased clinical benefit, progression-free survival, and superior quality of life in large, randomized phase III clinical trials, and additional VEGF pathway inhibitors are currently being studied. This review will summarize the major clinical trials and practical recommendations for the most studied VEGF inhibitors, including sunitinib, sorafenib, and bevacizumab; introduce novel VEGF inhibitor agents; outline side effects and toxicities; and discuss sequential and combination therapy with these agents.