Checkpoint Inhibitors for the Treatment of Renal Cell Carcinoma

The advent of checkpoint inhibitors has revolutionized systemic therapy for many malignancies, including renal cell carcinoma (RCC) where multiple PD-1, PD-L1, and CTLA-4 inhibitors have demonstrated responses and improved survival for patients in clinical trials. Durable benefit with manageable toxicity can be achieved with these agents—but unfortunately for only a minority of individuals. Efforts are ongoing to understand mechanisms driving the response and resistance to checkpoint inhibitors in order to personalize therapy and extend benefit to more patients. In particular, combination immunotherapy is an area of active study with multiple ongoing trials in RCC. Novel immunotherapeutic agents are being explored as well. Clinically, there are nuances related to the use of immunotherapy that are important to understand in order to provide optimal care to patients. Potential autoimmune toxicities are important to identify early so they can be best mitigated with immunosuppression, and careful review of imaging with clinical correlation is important to ensure responding patients are not taken off treatment prematurely due to “pseudo-progression.” Lastly, although immunotherapy is an important new tool, it exists among other active agents in the treatment of RCC, and further study is needed to understand where it best fits in the treatment paradigm. In this article, we review the most recent data for immune checkpoint inhibitors in metastatic renal cell carcinoma and more broadly discuss the rapidly evolving landscape of immunotherapy in RCC, including combination immunotherapies.