Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended 4-year follow-up of the phase III CheckMate 214 trial

Laurence Albiges*, Nizar M. Tannir, Mauricio Burotto, David McDermott, Elizabeth R. Plimack, Philippe Barthélémy, Camillo Porta, Thomas Powles, Frede Donskov, Saby George, Christian K. Kollmannsberger, Howard Gurney, Marc Oliver Grimm, Yoshihiko Tomita, Daniel Castellano, Brian I. Rini, Toni K. Choueiri, Shruti Shally Saggi, M. Brent McHenry, Robert J. Motzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

310 Scopus citations

Abstract

Purpose To report updated analyses of the phase III CheckMate 214 trial with extended minimum follow-up assessing long-Term outcomes with first-line nivolumab plus ipilimumab (NIVO+IPI) versus (vs) sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC). Methods Patients with aRCC with a clear cell component were stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk and randomised to NIVO (3 mg/kg) plus IPI (1 mg/kg) every three weeks ×4 doses, followed by NIVO (3 mg/kg) every two weeks; or SUN (50 mg) once per day ×4 weeks (6-week cycle). Efficacy endpoints included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) per independent radiology review committee in patients with intermediate/poor-risk disease (I/P; primary), intent-To-Treat patients (ITT; secondary) and in patients with favourable-risk disease (FAV; exploratory). Results Overall, 1096 patients were randomised (ITT: NIVO+IPI, n=550, SUN, n=546; I/P: NIVO+IPI, n=425, SUN, n=422; FAV: NIVO+IPI, n=125, SUN, n=124). After 4 years minimum follow-up, OS (HR; 95% CI) remained superior with NIVO+IPI vs SUN in ITT (0.69; 0.59 to 0.81) and I/P patients (0.65; 0.54 to 0.78). Four-year PFS probabilities were 31.0% vs 17.3% (ITT) and 32.7% vs 12.3% (I/P), with NIVO+IPI vs SUN. ORR remained higher with NIVO+IPI vs SUN in ITT (39.1% vs 32.4%) and I/P (41.9% vs 26.8%) patients. In FAV patients, the HRs (95% CI) for OS and PFS were 0.93 (0.62 to 1.40) and 1.84 (1.29 to 2.62); ORR was lower with NIVO+IPI vs SUN. However, more patients in all risk groups achieved complete responses with NIVO+IPI: ITT (10.7% vs 2.6%), I/P (10.4% vs 1.4%) and FAV (12.0% vs 6.5%). Probability (95% CI) of response ≥4 years was higher with NIVO+IPI vs SUN (ITT, 59% (0.51 to 0.66) vs 30% (0.21 to 0.39); I/P, 59% (0.50 to 0.67) vs 24% (0.14 to 0.36); and FAV, 60% (0.41 to 0.75) vs 38% (0.22 to 0.54)) regardless of risk category. Safety remained favourable with NIVO+IPI vs SUN. Conclusion After long-Term follow-up, NIVO+IPI continues to demonstrate durable efficacy benefits vs SUN, with manageable safety. Trial registration details ClinicalTrials.gov identifier: NCT02231749.

Original languageEnglish
Article numbere001079
JournalESMO Open
Volume5
Issue number6
DOIs
StatePublished - 27 Nov 2020
Externally publishedYes

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Keywords

  • advanced renal cell carcinoma
  • checkmate 214
  • dual checkpoint inhibition
  • long-Term follow-up
  • nivolumab plus ipilimumab

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