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Combination therapy for renal cell carcinoma: review of the clinical evidence

David F McDermott, Keith T Flaherty

The treatment of metastatic renal cell carcinoma has been revolutionized in recent years with the development of VEGF and mTOR targeted therapies. Individually, these agents have shown the ability to alter the natural history of this disease. While sequential single agent therapy appears to significantly prolong survival, patients still succumb to their disease eventually and further therapeutic advances are clearly needed. A detailed molecular understanding of the limits of the available therapies and the drivers of resistance to each is currently lacking. While those clinical investigations are undertaken, the field has turned its attention to the clinical evaluation of combination regimens containing individual drugs that have demonstrated efficacy in this disease. The largest number of such investigations has combined agents within the VEGF targeted class with mTOR inhibitors. However, there are reasons to believe that immunotherapy and chemotherapy combinations may also be relevant with this class of molecularly targeted agents. Although a number of recently completed clinical trials have provided insight into the limits of combination regimens built around VEGF targeted drugs, the results of several pending investigations will likely clarify the value of this approach.