Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial

Robert J Motzer, Brian I Rini, David F McDermott, Osvaldo Arén Frontera, Hans J Hammers, Michael A Carducci, Pamela Salman, Bernard Escudier, Benoit Beuselinck, Asim Amin, Camillo Porta, Saby George, Victoria Neiman, Sergio Bracarda, Scott S Tykodi, Philippe Barthélémy, Raya Leibowitz-Amit, Elizabeth R Plimack, Sjoukje F Oosting, Bruce RedmanBohuslav Melichar, Thomas Powles, Paul Nathan, Stéphane Oudard, David Pook, Toni K Choueiri, Frede Donskov, Marc-Oliver Grimm, Howard Gurney, Daniel Y C Heng, Christian K Kollmannsberger, Michael R Harrison, Yoshihiko Tomita, Ignacio Duran, Viktor Grünwald, M Brent McHenry, Sabeen Mekan, Nizar M Tannir, CheckMate 214 investigators

Research output: Contribution to journalArticle

Abstract

BACKGROUND: In the ongoing phase 3 CheckMate 214 trial, nivolumab plus ipilimumab showed superior efficacy over sunitinib in patients with previously untreated intermediate-risk or poor-risk advanced renal cell carcinoma, with a manageable safety profile. In this study, we aimed to assess efficacy and safety after extended follow-up to inform the long-term clinical benefit of nivolumab plus ipilimumab versus sunitinib in this setting. METHODS: In the phase 3, randomised, controlled CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced, or metastatic histologically confirmed renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by International Metastatic Renal Cell Carcinoma Database Consortium risk status into favourable-risk, intermediate-risk, and poor-risk subgroups and randomly assigned (1:1) to open-label nivolumab (3 mg/kg intravenously) plus ipilimumab (1 mg/kg intravenously) every 3 weeks for four doses, followed by nivolumab (3 mg/kg intravenously) every 2 weeks; or sunitinib (50 mg orally) once daily for 4 weeks (6-week cycle). Randomisation was done through an interactive voice response system, with a block size of four and stratified by risk status and geographical region. The co-primary endpoints for the trial were overall survival, progression-free survival per independent radiology review committee (IRRC), and objective responses per IRRC in intermediate-risk or poor-risk patients. Secondary endpoints were overall survival, progression-free survival per IRRC, and objective responses per IRRC in the intention-to-treat population, and adverse events in all treated patients. In this Article, we report overall survival, investigator-assessed progression-free survival, investigator-assessed objective response, characterisation of response, and safety after extended follow-up. Efficacy outcomes were assessed in all randomly assigned patients; safety was assessed in all treated patients. This study is registered with ClinicalTrials.gov, number NCT02231749, and is ongoing but now closed to recruitment. FINDINGS: Between Oct 16, 2014, and Feb 23, 2016, of 1390 patients screened, 1096 (79%) eligible patients were randomly assigned to nivolumab plus ipilimumab or sunitinib (550 vs 546 in the intention-to-treat population; 425 vs 422 intermediate-risk or poor-risk patients, and 125 vs 124 favourable-risk patients). With extended follow-up (median follow-up 32·4 months [IQR 13·4-36·3]), in intermediate-risk or poor-risk patients, results for the three co-primary efficacy endpoints showed that nivolumab plus ipilimumab continued to be superior to sunitinib in terms of overall survival (median not reached [95% CI 35·6-not estimable] vs 26·6 months [22·1-33·4]; hazard ratio [HR] 0·66 [95% CI 0·54-0·80], p
Original languageEnglish
Pages (from-to)1370-1385
Number of pages16
JournalThe Lancet. Oncology
Volume20
Issue number10
DOIs
Publication statusPublished - Oct 2019

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    Motzer, R. J., Rini, B. I., McDermott, D. F., Arén Frontera, O., Hammers, H. J., Carducci, M. A., Salman, P., Escudier, B., Beuselinck, B., Amin, A., Porta, C., George, S., Neiman, V., Bracarda, S., Tykodi, S. S., Barthélémy, P., Leibowitz-Amit, R., Plimack, E. R., Oosting, S. F., ... investigators, C. . (2019). Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. The Lancet. Oncology, 20(10), 1370-1385. https://doi.org/10.1016/S1470-2045(19)30413-9