Vascular endothelial growth factor-targeted therapy for the treatment of renal cell carcinoma

Vascular endothelial growth factor (VEGF)-targeted agents have rapidly been adopted into standard-of-care treatment for renal cell carcinoma (RCC). However, a substantial proportion of patients fail to respond to these agents or experience considerable toxicity. This article reviews the benefits and limitations of currently approved anti-VEGF agents in advanced and metastatic RCC, and the role for newly approved and developmental agents. Sunitinib and bevacizumab plus interferon (IFN)-α have demonstrated significant improvements in progression-free survival (PFS) compared with IFNα in treatment-nave patients. A PFS benefit has also been shown with sorafenib versus placebo second-line to cytokine therapy. However, no anti-VEGF agent has shown a significant overall survival benefit. Anti-VEGF therapy is generally well tolerated, but a number of key adverse events, including dermatological, mucosal and constitutional symptoms, may limit treatment compliance and success. Pazopanib is a recently approved, highly selective anti-VEGF agent that shows benefit in PFS over IFNα, with low rates of treatment-related adverse events and, therefore, may be better tolerated than other currently approved agents. The advent of VEGF-targeted therapy for RCC has greatly improved prospects for patients with advanced or metastatic disease, but more efficacious agents are required that demonstrate a clear survival advantage. Ongoing trials evaluating novel anti-VEGF therapies could establish whether the increased potency and selectivity of these agents results in improved efficacy and tolerability in RCC patients, further improving their prognosis.