Sequencing of agents for metastatic renal cell carcinoma: can we customize therapy?

CONTEXT: The expanding armamentarium of agents for the therapy of advanced clear cell renal cell carcinoma (RCC) warrants further investigation of optimal patient selection. OBJECTIVE: To analyze the second and subsequent line of targeted therapies for advanced RCC while integrating clinical and molecular markers and imaging. EVIDENCE ACQUISITION: Data were acquired from research published in peer-reviewed literature or presented at major conferences. EVIDENCE SYNTHESIS: Following first-line vascular endothelial growth factor (VEGF) inhibitors, second-line therapy with everolimus, a mammalian target of rapamycin inhibitor, and axitinib, a VEGF receptor tyrosine kinase inhibitor, have demonstrated benefits in progression-free survival (PFS). Sorafenib, pazopanib, and axitinib have demonstrated extension of PFS following cytokines. Optimal patient selection based on biomarkers is undergoing investigation. Clinical trials evaluating novel agents and combinations should be preferred. CONCLUSIONS: Currently, the sequence of therapy is based on patient and physician decision, which may be influenced by comorbidities and toxicity profiles.