Targeting the Pd-1 Pathway in Renal Cell Carcinoma: A Review

Abstract

Current systemic therapy for advanced renal cell carcinoma (RCC) includes a vascular endothelial growth factor receptor, tyrosine kinase inhibitors, and a mammalian target of rapamycin inhibitors. However, treatment outcomes are still poor in most of RCC. Immune checkpoints are one of the most promising immunotherapy approaches, and recently, nivolumab has been approved for this disease. In this review article, we have aimed to discuss the role of programmed cell death protein 1 (PD-1) and PD ligand 1 (PD-L1) in RCC and the efficacy and safety of immune checkpoints in the published or recently reported studies. The literature search was made from PubMed, ESMO and ASCO Annual Meetings abstracts by using the following search keywords: “renal cell carcinoma,” “kidney cancer,” “anti-PD-1 therapy,” “anti-PD-L1 therapy,” “nivolumab,” “pembrolizumab,” “avelumab,” and “atezolizumab.” The last search was on April 20, 2017. The limitation of our review is that most of the data in RCC are based on the phase I and II trials. Currently, the U.S. Food and Drug Administration and the European Medicines Agency have approved nivolumab, but an increasing number of trials investigating the PD-1 pathway are ongoing with promising and encouraging results. According to early results of published trials, the response to anti-PD1 /PD-L1 agents is not clearly associated with PD-L1 expression. Nivolumab showed promising efficacy with acceptable safety data in metastatic RCC. Given the encouraging clinical activity and safety profile of the current PD-1/PD-L1 inhibitors, it is likely that combination approaches will take a major role in the near future.