Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma

Robert J. Motzer*, David F. McDermott, Bernard Escudier, Mauricio Burotto, Toni K. Choueiri, Hans J. Hammers, Philippe Barthélémy, Elizabeth R. Plimack, Camillo Porta, Saby George, Thomas Powles, Frede Donskov, Howard Gurney, Christian K. Kollmannsberger, Marc Oliver Grimm, Carlos Barrios, Yoshihiko Tomita, Daniel Castellano, Viktor Grünwald, Brian I. RiniM. Brent McHenry, Chung Wei Lee, Jennifer McCarthy, Flavia Ejzykowicz, Nizar M. Tannir

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Conditional survival estimates provide critical prognostic information for patients with advanced renal cell carcinoma (aRCC). Efficacy, safety, and conditional survival outcomes were assessed in CheckMate 214 (ClinicalTrials.gov identifier NCT02231749) with a minimum follow-up of 5 years. Methods: Patients with untreated aRCC were randomized to receive nivolumab (NIVO) (3 mg/kg) plus ipilimumab (IPI) (1 mg/kg) every 3 weeks for 4 cycles, then either NIVO monotherapy or sunitinib (SUN) (50 mg) daily (four 6-week cycles). Efficacy was assessed in intent-to-treat, International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk/poor-risk, and favorable-risk populations. Conditional survival outcomes (the probability of remaining alive, progression free, or in response 2 years beyond a specified landmark) were analyzed. Results: The median follow-up was 67.7 months; overall survival (median, 55.7 vs 38.4 months; hazard ratio, 0.72), progression-free survival (median, 12.3 vs 12.3 months; hazard ratio, 0.86), and objective response (39.3% vs 32.4%) benefits were maintained with NIVO+IPI versus SUN, respectively, in intent-to-treat patients (N = 550 vs 546). Point estimates for 2-year conditional overall survival beyond the 3-year landmark were higher with NIVO+IPI versus SUN (intent-to-treat patients, 81% vs 72%; intermediate-risk/poor-risk patients, 79% vs 72%; favorable-risk patients, 85% vs 72%). Conditional progression-free survival and response point estimates were also higher beyond 3 years with NIVO+IPI. Point estimates for conditional overall survival were higher or remained steady at each subsequent year of survival with NIVO+IPI in patients stratified by tumor programmed death ligand 1 expression, grade ≥3 immune-mediated adverse event experience, body mass index, and age. Conclusions: Durable clinical benefits were observed with NIVO+IPI versus SUN at 5 years, the longest phase 3 follow-up for a first-line checkpoint inhibitor-based combination in patients with aRCC. Conditional estimates indicate that most patients who remained alive or in response with NIVO+IPI at 3 years remained so at 5 years.

Original languageEnglish
Pages (from-to)2085-2097
Number of pages13
JournalCancer
Volume128
Issue number11
DOIs
StateAccepted/In press - 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Keywords

  • advanced renal cell carcinoma
  • CheckMate 214
  • dual checkpoint inhibition
  • durable response
  • long-term follow-up
  • nivolumab plus ipilimumab
  • phase 3

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