Immunotherapy for Renal Cancer: Sequencing and Combinations.

CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated.

OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC.

EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena.

EVIDENCE SYNTHESIS: The favorable therapeutic index of programmed cell death 1/programmed death-ligand 1 inhibitors enable combinations of these agents. Multiple ongoing phase 3 trials are evaluating the first-line therapy of RCC using a combination of programmed cell death 1/programmed death-ligand 1 inhibitors with vascular endothelial growth factor inhibitors or cytotoxic T-lymphocyte-associated protein 4 inhibitors. The role of sequencing using single agent sunitinib and avelumab will be evaluated in a randomized phase 2 trial. The role of vaccine therapy remains unproven. The role of predictive biomarkers to select appropriate therapy requires a greater focus, given the multitude of possible therapies.

CONCLUSIONS: Therapy for RCC should be tailored based on both patient and tumor characteristics. Combination therapy and sequencing of single agents may both play roles and are currently undergoing clinical trial evaluation.

PATIENT SUMMARY: Combinations of immunotherapy with angiogenesis inhibitors are undergoing vigorous clinical trial evaluations. Sequencing of immunotherapy and antiangiogenic therapy is also undergoing investigation. Clinical trial participation is critically important to develop new drugs and combinations, and biomarkers to select therapy.