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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • 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

OriginalsprogEngelsk
TidsskriftClinical Cancer Research
Vol/bind27
Nummer1
Sider (fra-til)78-86
ISSN1078-0432
DOI
StatusUdgivet - jan. 2021

Bibliografisk note

Funding Information:
employers) during the conduct of the study; grants and personal fees from Genentech/ Roche (paid consultancy to self and grant support to employer), Merck (paid consultancy to self and grant support to employer), Pfizer (paid consultancy to self and grant support to employer), Eisai (paid consultancy to self and grant support to employer), and Exelixis (paid consultancy to self and grant support to employer); grants from AstraZeneca (paid consultancy to self) and grants and personal fees from Novartis (paid consultancy to self and grant support to employer) outside the submitted work. J.-C. Pignon reports personal fees from Bristol Myers Squibb (current consultant for BMS) outside the submitted work. S. George reports grants and personal fees from Bayer (institutional grant), BMS (institutional grant), Corvus (institutional grant), Eisai (institutional grant), Merck (institutional grant), Pfizer (institutional grant), and Seattle Genetics (institutional grant); personal fees from Sanofi, Exelixis, Genentech, and EMD Serono; grants from Agensys (institutional grant), Immunomedics (institutional grant), Calithera (institutional grant), and Novartis (institutional grant) outside the submitted work. T. Powles reports grants and personal fees from AstraZeneca and Roche; personal fees from BMS, MSD, Novartis, Pfizer, Exelixis, and Merck Serono during the conduct of the study. F. Donskov reports grants from Pfizer (to institution), MSD (to institution), and Ipsen (to institution) outside the submitted work. M.R. Harrison reports grants from Bristol Myers Squibb (research funding to institution) during the conduct of the study; grants from Acerta, Astellas, Clovis Oncology, and Merck; grants and personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Exelixis, Genentech, and Pfizer; personal fees from FujiFilm and Janssen, and grants from Seattle Genetics outside the submitted work. P. Barthélémy reports other from BMS (consulting, travel) during the conduct of the study; other from MSD (consulting, travel), Pfizer (consulting, travel), Ipsen (consulting, travel), Janssen Cilag (consulting, travel), AstraZeneca (consulting), Amgen (consulting, travel), Novartis (consulting), Eusapharma (consulting), Roche (consulting, travel), and Astellas (consulting, travel) outside the submitted work. S.S. Tykodi reports other from Bristol Myers Squibb (clinical trial support received on behalf of my institution) and nonfinancial support from Bristol Myers Squibb (manuscript preparation) during the conduct of the study; other from Merck (clinical trial support received on behalf of my institution), Merck (consultant), Nektar Therapeutics (clinical trial support received on behalf of my institution), Jounce Therapeutics (clinical trial support received on behalf of my institution), Pfizer (clinical trial support received on behalf of my institution), Clinigen (clinical trial support received on behalf of my institution), Exelixis (clinical trial support received on behalf of my institution), Genentech (clinical trial support received on behalf of my institution), and Calithera Biosciences (clinical trial support received on behalf of my institution) outside the submitted work. A. Ravaud reports personal fees and nonfinancial support from Pfizer, Merck, MSD, Ipsen, BMS, and Roche during the conduct of the study; grants, personal fees, and nonfinancial support from Pfizer and Merck; and personal fees and nonfinancial support from AstraZeneca outside the submitted work. J.R. Rodriguez-Cid reports other from Bristol Myers Squibb (trial funding) during the conduct of the study; and other Bristol Myer Squibb (trials funding, speaker, advisory), Roche (trials funding, speaker, advisory), MSD (trials funding, speaker, advisory), Novartis (trials funding, speaker, advisory), Boehinger Ingelheim (trials funding, speaker, advisory), Takeda (trials funding, speaker, advisory), Pfizer (speaker, advisory), Bayer (speaker, advisory), Celltrion (trials funding), Sanofi Aventis (speaker, advisory), Janssen (trials funding), and AstraZeneca (trials funding, speaker, advisory) outside the submitted work. S.K. Pal reports personal fees from Novartis, Aveo, Genentech, Bristol Myers Squibb, Astellas Pharma, Eisai, Roche, Ipsen, and Medivation outside the submitted work. Y. Ishii reports being a BMS employee. S.S. Saggi reports other from Bristol Myers Squibb (employee) outside the submitted work. M.B. McHenry reports being a BMS employee and owning BMS stock. B.I. Rini reports grants and personal fees from BMS during the conduct of the study; grants, personal fees, and nonfinancial support from Merck and Pfizer; grants

Funding Information:
This work was supported by Bristol Myers Squibb (Princeton, NJ) and ONO Pharmaceutical Company Ltd. (Osaka, Japan). Authors received no financial support or compensation for publication of this article. The University of Texas MD Anderson Cancer Center is supported by the NIH (grant no. P30 CA016672). Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant (Core grant number P30 CA008748).

Funding Information:
N.M. Tannir reports grants from Bristol Myers Squibb during the conduct of the study; grants and personal fees from Exelixisa and Nektar Therapeutics; grants from Calithera Bioscience, Takeda, Arrowhead Pharmaceuticals, and Epizyme, Inc.; personal fees from Bristol Myers Squibb, Pfizer, Lilly Oncology, Neolukin Therapeutics, Eisai, Novartis, Oncorena, Ono Pharmaceutical, Surface Oncology, and Ipsen outside the submitted work. S. Signoretti reports grants and personal fees from Bristol Myers Squibb during the conduct of the study; and grants and personal fees from AstraZeneca; grants from Exelixis and Novartis; personal fees from Merck, CRISPR Therapeutics AG, AACR, and NCI outside the submitted work, and received royalties from Biogenex related to their CDX2 antibody. T.K. Choueiri reports grants, personal fees, nonfinancial support, and other from BMS, Merck, Roche, Pfizer, EMD, Exelixis, Novartis, and AstraZeneca [advisory board, consultancy, honorarium, payments (personal and for institution)], and a patent for IO biomarkers pending, issued, and licensed to DFCI (related to IO). D.F. McDermott reports personal fees from BMS (advisory board participant) during the conduct of the study; personal fees from Merck, Genentech, and Pfizer outside the submitted work. R.J. Motzer reports grants and other from Bristol Myers Squibb (travel expense to author and grant support to

Funding Information:
The patients and families who made this study possible. The clinical study teams who participated in the study. The study was supported by Bristol Myers Squibb. All authors contributed to and approved the presentation; writing and editorial assistance was provided by Rachel Lieberman, PhD, of Parexel, funded by Bristol Myers Squibb. Dako, an Agilent Technologies, Inc. company, for collaborative development of the PD-L1 IHC 28-8 pharmDx assay (Santa Clara, CA). Bristol Myers Squibb (Princeton, NJ) and ONO Pharmaceutical Company Ltd. (Osaka, Japan).

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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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