ESMO Virtual Congress 2020: Nivolumab + Ipilimumab vs. Sunitinib for First-Line Treatment of Advanced Renal Cell Carcinoma in CheckMate 214: 4-Year Follow-up and Subgroup Analysis of Patients without Nephrectomy

(UroToday.com) The treatment landscape for first-line therapy among patients with metastatic renal cell carcinoma (mRCC) has changed dramatically over the past 2 years. In 2018, publication of the CheckMate214 data demonstrated a survival benefit for patients treated with nivolumab and ipilimumab compared with sunitinib in intermediate and poor-risk mRCC, ushering in the immunotherapy era for mRCC. The subsequent publication of the JAVELIN Renal 101 and KEYNOTE-426 studies in 2019 demonstrated superiority of avelumab and axitinib and pembrolizumab and axitinib, compared to sunitinib in this disease space. These two trials were the first to demonstrate that the combination of immunotherapy with checkpoint inhibition and targeted therapy improved overall survival compared to sunitinib, the previous standard of care. Network meta-analysis following the publication of these data demonstrated the apparent superiority of this combined approach.


In a poster presentation at this year’s European Society of Medical Oncology (ESMO) 2020 Virtual Annual Meeting, Dr. Laurence Albiges presented long-term data of the CheckMate214 trial comparing nivolumab and ipilimumab to sunitinib, with a focus on the subgroup of patients without a history of prior nephrectomy.

To briefly summarize the design of CheckMate 214, patients with advanced clear cell renal cell carcinoma were randomized in a 1:1 fashion to nivolumab 3mg/kg and ipilimumab 1mg/kg x 4 cycles followed by nivolumab or to sunitinib 50mg PO daily on a 4 week on / 2 week off schedule.

Primary outcomes measures include Overall Survival (OS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC), Investigator-assessed Objective Response Rate(ORR) in Intermediate/Poor Risk Participants as well as, Progression-Free Survival (PFS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC).

This data presented at ESMO represented an updated analysis of patients with at least 4 years of follow-up. In the intention-to-treat population, the combined nivolumab/ipilimumab approach continued to demonstrate superiority (hazard ratio 0.69, 95% confidence interval 0.59 to 0.81). In sub-groups defined according to IMDC criteria, those with intermediate or poor-risk had improved survival with nivolumab/ipilimumab (hazard ratio 0.65, 95% confidence interval 0.54 to 0.78) while there was no appreciable difference among those with favorable-risk disease (hazard ratio 0.93, 95% confidence interval 0.62 to 1.40). Similar benefits in objective response rate were also seen.

The authors then presented post hoc analyses of patients without a history of nephrectomy for whom a target kidney lesion could be identified. Primary tumor responses were more common among patients receiving nivolumab/ipilimumab. Notably, no complete responses were seen.

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Among patients with a target kidney lesion, median overall survival was longer among those randomized to nivolumab/ipilimumab (26.1 months, 95% confidence interval 13.9 to 35.4) as compared to sunitinib (14.3 months, 95% confidence interval 9.7 to 22.6) (hazard ratio 0.63, 95% confidence interval 0.40 to 1.00).

Presented by: Laurence Albiges, MD, Ph.D., Medical Oncologist, Department of Cancer Medicine, Institut Gustave Roussy

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center (@WallisCJD on Twitter) at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept - 21 Sept 2020 


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ASCO GU 2020: Overall Survival and Independent Review of Response in CheckMate 214 with 42-month Follow-up: First-line Nivolumab + Ipilimumab versus Sunitinib in Patients with Advanced Renal Cell Carcinoma