ASCO GU 2018: Characterization of the Benefit-Risk Profile of Nivolumab + Ipilimumab Sunitinib for Treatment-Naïve Advanced RCC (Checkmate 214)

San Francisco, CA ( Dr. Nizar Tannir presented on the characterization of the benefit-risk profile of nivolumab + ipilimumab vs sunitinib in the CheckMate 214 study. This study assessed nivolumab + ipilimumab vs sunitinib in the first line setting of metastatic RCC, noting a significant overall survival advantage for nivolumab + ipilimumab [1]. The objective of this study was to report additional data and define the benefit risk of nivolumab + ipilimumab, considering that in addition to a survival advantage, the immunotherapy regimen was well tolerated with acceptable safety considerations. 

Patients in CheckMate 214 all had advanced clear-cell RCC and randomized 1:1 to nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg daily orally for 4 weeks (6-week cycles). The primary endpoints were efficacy parameters in intermediate/poor-risk patients. Secondary endpoints included adverse event incidence in all treated patients. Select adverse events were defined and pooled by organ category that may differ from adverse events caused by non-immunotherapies, may require immunosuppression, and whose early recognition may mitigate severe toxicity.

Among the 1,096 patients in CheckMate 214, there were 547 patients that received nivolumab + ipilimumab and 535 patients that received sunitinib. Seventy-nine percent of nivolumab + ipilimumab patients received all four ipilimumab doses. Drug-related grade 3-5 adverse events occurred in 46% of patients treated with nivolumab + ipilimumab, compared to 63% with sunitinib. Drug-related adverse events leading to discontinuation occurred in 22% of nivolumab + ipilimumab patients vs 12% for sunitinib. Drug-related select adverse events resolved in 72%-92% of nivolumab + ipilimumab patients, except for endocrinopathies (43%). 

A full list of drug-related select adverse events:
Abstract 686 1

Dr. Tannir concluded that drug-related select adverse events with nivolumab + ipilimumab are manageable, with the vast majority resolving except for endocrinopathies. This additional data further support the favorable benefit-risk profile of nivolumab + ipilimumab initially reported in CheckMate 214. 

Clinical trial: NCT02231749

Presented by: Nizar Tannir, MD, FACP, MD Anderson Cancer Center, Houston, TX

Hans J. Hammers, Asim Amin, Marc-Oliver Grimm, Brian I. Rini, Sabeen Mekan, M. Brent McHenry, Christian K. Kollmannsberger; UT MD Anderson Cancer Center, Houston, TX; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC; University Hospital Jena, Jena, Germany; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bristol-Myers Squibb, Lawrenceville, NJ; Bristol-Myers Squibb, Wallingford, CT; British Columbia Cancer Agency - Vancouver Centre, Vancouver, BC, Canada

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, @zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA


1. Escudier B, Tannir N, McDermott D, et al. CheckMate 214: Efficacy and safety of Nivolumab + Ipilimumab vs Sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. ESMO 2017 abst LBA5.