Nivolumab in renal cell carcinoma

Immune-based therapies (e.g., IL-2, IFN) have been used for some time in advanced clear cell renal cell carcinoma (RCC) with overall modest success. Recent advances have demonstrated that tumor cells evade immune-mediated destruction by inducing inhibitory signals that result in effector T-cell exhaustion. One mechanism involves interaction between the T-cell programmed death-1 (PD-1) receptor and its ligand, PD ligand-1, expressed on tumor and inflammatory cells. Nivolumab , an anti-PD-1 antibody, blocks this pathway, thereby reversing T-cell suppression and activating antitumor responses.

In this review, the authors summarize selected aspects of PD-1 signaling, the development of immune checkpoint therapeutic agents, and clinical data regarding the safety and efficacy of nivolumab in RCC from Phase I and II clinical trials.

Objective responses and safety profiles of single-agent nivolumab are favorable in patients with previously treated and treatment-naive metastatic RCC. Combination therapies involving nivolumab are ongoing and have generated encouraging results. The use of nivolumab will have substantial impact on the management of patients with RCC.