TY - JOUR
T1 - Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma
AU - Motzer, Robert J.
AU - McDermott, David F.
AU - Escudier, Bernard
AU - Burotto, Mauricio
AU - Choueiri, Toni K.
AU - Hammers, Hans J.
AU - Barthélémy, Philippe
AU - Plimack, Elizabeth R.
AU - Porta, Camillo
AU - George, Saby
AU - Powles, Thomas
AU - Donskov, Frede
AU - Gurney, Howard
AU - Kollmannsberger, Christian K.
AU - Grimm, Marc Oliver
AU - Barrios, Carlos
AU - Tomita, Yoshihiko
AU - Castellano, Daniel
AU - Grünwald, Viktor
AU - Rini, Brian I.
AU - McHenry, M. Brent
AU - Lee, Chung Wei
AU - McCarthy, Jennifer
AU - Ejzykowicz, Flavia
AU - Tannir, Nizar M.
N1 - Publisher Copyright:
© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - advanced renal cell carcinoma
KW - CheckMate 214
KW - dual checkpoint inhibition
KW - durable response
KW - long-term follow-up
KW - nivolumab plus ipilimumab
KW - phase 3
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U2 - 10.1002/cncr.34180
DO - 10.1002/cncr.34180
M3 - Article
C2 - 35383908
AN - SCOPUS:85127785977
SN - 0008-543X
VL - 128
SP - 2085
EP - 2097
JO - Cancer
JF - Cancer
IS - 11
ER -