Efficacy and safety of nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma

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  • Nizar M. Tannir, University of Texas MD Anderson Cancer Center
  • ,
  • Sabina Signoretti, Harvard University, Dana-Farber Cancer Institute
  • ,
  • Toni K. Choueiri, Dana-Farber Cancer Institute
  • ,
  • David F. McDermott, Dana-Farber/Harvard Cancer Center
  • ,
  • Robert J. Motzer, Memorial Sloan-Kettering Cancer Center
  • ,
  • Abdallah Flaifel, Harvard University
  • ,
  • Jean Christophe Pignon, Harvard University
  • ,
  • Miriam Ficial, Harvard University
  • ,
  • Osvaldo Aren Frontera, Centro de Investigacion Clínica Bradford Hill
  • ,
  • Saby George, Roswell Park Cancer Institute
  • ,
  • Thomas Powles, Queen Mary University of London
  • ,
  • Frede Donskov
  • Michael R. Harrison, Duke University
  • ,
  • Philippe Barthel Emy, Université de Strasbourg
  • ,
  • Scott S. Tykodi, University of Washington
  • ,
  • Judit Kocsis, University of Debrecen, Bács-Kiskun County Hospital
  • ,
  • Alain Ravaud, CHU de Bordeaux
  • ,
  • Jeronimo R. Rodriguez-Cid, Hospital Médica Sur
  • ,
  • Sumanta K. Pal, City of Hope National Med Center
  • ,
  • Andre M. Murad, CENANTRON-PERSONAL-Precision Oncology
  • ,
  • Yuko Ishii, Bristol-Myers Squibb
  • ,
  • Shruti Shally Saggi, Bristol-Myers Squibb
  • ,
  • M. Brent McHenry, Bristol-Myers Squibb
  • ,
  • Brian I. Rini, Vanderbilt University

Purpose: Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognoses and suboptimal outcomes with targeted therapy. This post hoc analysis of the phase III CheckMate 214 trial analyzed the efficacy of nivolumab plus ipilimumab (NIVOþIPI) versus sunitinib in patients with sRCC. Patients and Methods: Patients with sRCC were identified via independent central pathology review of archival tumor tissue or histologic classification per local pathology report. Patients were randomized 1:1 to receive nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks (four doses) then nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg orally every day (4 weeks; 6-week cycles). Outcomes in patients with sRCC were not prespecified. Endpoints in patients with sRCC and International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk disease included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Safety outcomes used descriptive statistics. Results: Of 1,096 randomized patients in CheckMate 214, 139 patients with sRCC and intermediate/poor-risk disease and six with favorable-risk disease were identified. With 42 months' minimum follow-up in patients with sRCC and intermediate/poor-risk disease, median OS [95% confidence interval (CI)] favored NIVOþIPI [not reached (NR) (25.2-not estimable [NE]); n ¼ 74] versus sunitinib [14.2 months (9.3–22.9); n ¼ 65; HR, 0.45 (95% CI, 0.3–0.7; P ¼ 0.0004)]; PFS benefits with NIVOþIPI were similarly observed [median 26.5 vs. 5.1 months; HR, 0.54 (95% CI, 0.33–0.86; P ¼ 0.0093)]. Confirmed ORR was 60.8% with NIVOþIPI versus 23.1% with sunitinib, with complete response rates of 18.9% versus 3.1%, respectively. No new safety signals emerged. Conclusions: NIVOþIPI showed unprecedented long-term survival, response, and complete response benefits versus sunitinib in previously untreated patients with sRCC and intermediate/poor-risk disease, supporting the use of first-line NIVOþIPI for this population. See related commentary by Hwang et al., p. 5

Original languageEnglish
JournalClinical Cancer Research
Volume27
Issue1
Pages (from-to)78-86
ISSN1078-0432
DOIs
Publication statusPublished - Jan 2021

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© 2020 American Association for Cancer Research.

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Copyright 2021 Elsevier B.V., All rights reserved.

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