• Xin Gao and David F McDermott.
• a Department of Medicine , Massachusetts General Hospital , Boston , MA , USA.
• Expert Opin Biol Ther. 2018 Sep 1; 18 (9): 947-957.

IntroductionRenal cell carcinoma (RCC) is a highly immunogenic neoplasm, and cytokine-based immunotherapies have been used for decades with limited success. In recent years, antibody-based immunotherapies targeting immune checkpoint receptors PD-1 and CTLA-4 have demonstrated clinical efficacy in metastatic RCC (mRCC) patients, leading to FDA approval of the combination of nivolumab and ipilimumab in treatment-naïve patients with intermediate- or poor-risk disease in April 2018. Areas covered: The pharmacodynamics and pharmacokinetics of nivolumab and ipilimumab are reviewed. Clinical safety and efficacy results from pivotal phase I and III trials of the combination of nivolumab plus ipilimumab in mRCC are summarized, and the combination is reviewed in the context of other available systemic therapies for RCC. Ongoing clinical studies involving the combination of nivolumab plus ipilimumab in RCC are discussed. Expert opinion: The combination of nivolumab and ipilimumab has demonstrated superior efficacy for treatment-naïve patients with intermediate- and poor-risk mRCC with clear cell histology and is likely to replace anti-angiogenic therapies as the treatment-of-choice in this patient population in the United States. Development of additional combination strategies, novel trial designs, and predictive biomarkers of response will be important to further optimize therapeutic selection and clinical outcomes.

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