Novel Agents and Approaches for Advanced Renal Cell Carcinoma

Purpose: Targeted agents have changed the treatment paradigm for advanced renal cell carcinoma. Approved agents with demonstrated efficacy are sunitinib, sorafenib, pazopanib, bevacizumab, temsirolimus and everolimus. However, there is an unmet need for new agents to improve the clinical outcome in treatment naive patients and in those who are disease refractory or intolerant to traditional and targeted therapies. Many novel targeted agents, of which some have different mechanisms of action than approved agents, and immunomodulatory agents are currently in development for renal cell carcinoma. Materials and Methods: We searched ClinicalTrials.gov to identify novel agents for advanced renal cell carcinoma in ongoing phase II/III clinical trials. Using the relevant agents as search terms we reviewed the medical literature for mechanisms of action and efficacy, and safety results to date, including data from recent major oncology meetings. Results: A total of 11 novel targeted agents, including next generation tyrosine kinase inhibitors, and inhibitors of vascular endothelial growth factor ligand binding, Akt and endothelial cell proliferation, and 3 novel immunomodulatory agents, are under evaluation for renal cell carcinoma. In addition to ongoing phase II/III trials of emerging agents, head-to-head, crossover and combination trials of approved targeted agents are under way. Conclusions: Although many agents are approved or in development for renal cell carcinoma, comparative effectiveness data are lacking. Ongoing and future head-to-head trials using appropriate comparators are essential to update renal cell carcinoma treatment guidelines. Future research should be aimed at identifying agents that improve patient outcomes and have decreased toxicity compared with currently approved agents with the goal of complete remission.