Ipilimumab in combination with nivolumab for the treatment of renal cell carcinoma

ABSTRACT

Introduction: Renal 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.

KEYWORDS:

• CTLA-4
• immune checkpoint therapy
• ipilimumab
• kidney cancer
• nivolumab
• PD-1
• renal cell carcinoma

Box 1. Drug summary box

Acknowledgments

The authors thank Jane Hayward of the Beth Israel Deaconess Medical Center Media Services for her assistance with the production of Figure 1 for this article.

Declaration of interest

DF McDermott has received honoraria in consultancy for Bristol-Myers Squibb, Pfizer, Merck, Novartis, Eisai, Exelixis, Array BioPharma, and Genentech. DF McDermott has received research support from Bristol-Myers Squibb and Prometheus Laboratories. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported in part by NIH/NCI Dana-Farber/Harvard Cancer Center (DF/HCC) Kidney Cancer SPORE P50 CA101942.