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Targeted Therapy for Metastatic Renal Cell Carcinoma

Robert J. Motzer, Ronald M. Bukowski

From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, the Memorial Sloan-Kettering Cancer Center, New York, NY; and the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and the Cleveland Clinic Foundation, Cleveland, OH

Address reprint requests to Robert J. Motzer, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; e-mail: motzerr{at}mskcc.org

The discovery of a relationship for the VHL tumor suppressor gene, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor in the growth of clear-cell renal cell carcinoma (RCC) has identified a pathway for novel targeted therapy. This study evaluated the impact of these agents on metastatic RCC (mRCC), and highlights recent phase II and III trials. A systematic review examined the clinical data for novel targeted agents in mRCC, with a focus on randomized phase II and III trials of the novel targeted agents sunitinib, temsirolimus, sorafenib, and bevacizumab. Several agents, including the small-molecule targeted inhibitors sunitinib, temsirolimus, sorafenib, and the monoclonal antibody bevacizumab, have demonstrated antitumor activity in randomized trials. Superior activity was found with sunitinib and temsirolimus versus cytokines in first-line therapy. Improved progression-free survival was reported with sorafenib and bevacizumab given second-line compared with placebo. Targeted therapies show promising activity in this disease, and they have been changing patient management. Sunitinib and sorafenib were recently approved by the US Food and Drug Administration for treatment of mRCC, These drugs are currently included in clinical practice.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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