Robert J Motzer1, Bernard Escudier, David F McDermott, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Giuseppe Procopio, Elizabeth R Plimack, Daniel Castellano, Toni K Choueiri, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas C Gauler, Takeshi Ueda, Yoshihiko Tomita, Fabio A Schutz, Christian Kollmannsberger, James Larkin, Alain Ravaud, Jason S Simon, Li-An Xu, Ian M Waxman, Padmanee Sharma. 1. From Memorial Sloan Kettering Cancer Center, New York (R.J.M.), and Roswell Park Cancer Institute, Buffalo (S.G.) - both in New York; Institut Gustave Roussy, Villejuif (B.E.), and Bordeaux University Hospital, Hôpital Saint André, Bordeaux (A.R.) - both in France; Beth Israel Deaconess Medical Center (D.F.M.) and Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School (T.K.C.) - all in Boston; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore (H.J.H.); Stanford Cancer Institute, Stanford, CA (S.S.); University of Washington and Fred Hutchinson Cancer Research Center, Seattle (S.S.T.); Vanderbilt University Medical Center, Nashville (J.A.S.); Fondazione Istituto Nazionale Tumori, Milan (G.P.); Fox Chase Cancer Center, Philadelphia (E.R.P.); Hospital Universitario 12 De Octubre, Madrid (D.C.); Westmead Hospital and Macquarie University, Sydney (H.G.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Helsinki University Central Hospital and University of Helsinki, Helsinki (P.B.); South West Wales Cancer Institute and Swansea University College of Medicine, Swansea (J.W.), and Royal Marsden Hospital, London (J.L.) - both in the United Kingdom; University Hospital Essen of University of Duisburg-Essen, Germany (T.C.G.); Chiba Cancer Center, Chiba (T.U.), and Niigata University, Niigata (Y.T.) - both in Japan; Hospital Sao Jose, Beneficencia Portuguesa de São Paulo, São Paulo (F.A.S.); British Columbia Cancer Agency, Vancouver, BC, Canada (C.K.); Bristol-Myers Squibb, Lawrenceville (J.S.S., I.M.W.) and Hopewell (L.-A.X.) - both in New Jersey; and M.D. Anderson Cancer Center, University of Texas, Houston (P.S.).
Abstract
BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens ofantiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. RESULTS: The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%). CONCLUSIONS: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).
RCT Entities:
BACKGROUND:Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. RESULTS: The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%). CONCLUSIONS: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).
Authors: R Houston Thompson; Michael D Gillett; John C Cheville; Christine M Lohse; Haidong Dong; W Scott Webster; Kent G Krejci; John R Lobo; Shomik Sengupta; Lieping Chen; Horst Zincke; Michael L Blute; Scott E Strome; Bradley C Leibovich; Eugene D Kwon Journal: Proc Natl Acad Sci U S A Date: 2004-11-29 Impact factor: 11.205
Authors: Julie R Brahmer; Charles G Drake; Ira Wollner; John D Powderly; Joel Picus; William H Sharfman; Elizabeth Stankevich; Alice Pons; Theresa M Salay; Tracee L McMiller; Marta M Gilson; Changyu Wang; Mark Selby; Janis M Taube; Robert Anders; Lieping Chen; Alan J Korman; Drew M Pardoll; Israel Lowy; Suzanne L Topalian Journal: J Clin Oncol Date: 2010-06-01 Impact factor: 44.544
Authors: Suzanne L Topalian; F Stephen Hodi; Julie R Brahmer; Scott N Gettinger; David C Smith; David F McDermott; John D Powderly; Richard D Carvajal; Jeffrey A Sosman; Michael B Atkins; Philip D Leming; David R Spigel; Scott J Antonia; Leora Horn; Charles G Drake; Drew M Pardoll; Lieping Chen; William H Sharfman; Robert A Anders; Janis M Taube; Tracee L McMiller; Haiying Xu; Alan J Korman; Maria Jure-Kunkel; Shruti Agrawal; Daniel McDonald; Georgia D Kollia; Ashok Gupta; Jon M Wigginton; Mario Sznol Journal: N Engl J Med Date: 2012-06-02 Impact factor: 91.245
Authors: R Houston Thompson; Susan M Kuntz; Bradley C Leibovich; Haidong Dong; Christine M Lohse; W Scott Webster; Shomik Sengupta; Igor Frank; Alexander S Parker; Horst Zincke; Michael L Blute; Thomas J Sebo; John C Cheville; Eugene D Kwon Journal: Cancer Res Date: 2006-04-01 Impact factor: 12.701
Authors: Robert J Motzer; Jennifer Bacik; Lawrence H Schwartz; Victor Reuter; Paul Russo; Stephanie Marion; Madhu Mazumdar Journal: J Clin Oncol Date: 2004-02-01 Impact factor: 44.544
Authors: David Cella; Susan Yount; Penny S Brucker; Hongyan Du; Ronald Bukowski; Nicholas Vogelzang; William P Bro Journal: Value Health Date: 2007 Jul-Aug Impact factor: 5.725
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Shona Hendry; Roberto Salgado; Thomas Gevaert; Prudence A Russell; Tom John; Bibhusal Thapa; Michael Christie; Koen van de Vijver; M V Estrada; Paula I Gonzalez-Ericsson; Melinda Sanders; Benjamin Solomon; Cinzia Solinas; Gert G G M Van den Eynden; Yves Allory; Matthias Preusser; Johannes Hainfellner; Giancarlo Pruneri; Andrea Vingiani; Sandra Demaria; Fraser Symmans; Paolo Nuciforo; Laura Comerma; E A Thompson; Sunil Lakhani; Seong-Rim Kim; Stuart Schnitt; Cecile Colpaert; Christos Sotiriou; Stefan J Scherer; Michail Ignatiadis; Sunil Badve; Robert H Pierce; Giuseppe Viale; Nicolas Sirtaine; Frederique Penault-Llorca; Tomohagu Sugie; Susan Fineberg; Soonmyung Paik; Ashok Srinivasan; Andrea Richardson; Yihong Wang; Ewa Chmielik; Jane Brock; Douglas B Johnson; Justin Balko; Stephan Wienert; Veerle Bossuyt; Stefan Michiels; Nils Ternes; Nicole Burchardi; Stephen J Luen; Peter Savas; Frederick Klauschen; Peter H Watson; Brad H Nelson; Carmen Criscitiello; Sandra O'Toole; Denis Larsimont; Roland de Wind; Giuseppe Curigliano; Fabrice André; Magali Lacroix-Triki; Mark van de Vijver; Federico Rojo; Giuseppe Floris; Shahinaz Bedri; Joseph Sparano; David Rimm; Torsten Nielsen; Zuzana Kos; Stephen Hewitt; Baljit Singh; Gelareh Farshid; Sibylle Loibl; Kimberly H Allison; Nadine Tung; Sylvia Adams; Karen Willard-Gallo; Hugo M Horlings; Leena Gandhi; Andre Moreira; Fred Hirsch; Maria V Dieci; Maria Urbanowicz; Iva Brcic; Konstanty Korski; Fabien Gaire; Hartmut Koeppen; Amy Lo; Jennifer Giltnane; Marlon C Rebelatto; Keith E Steele; Jiping Zha; Kenneth Emancipator; Jonathan W Juco; Carsten Denkert; Jorge Reis-Filho; Sherene Loi; Stephen B Fox Journal: Adv Anat Pathol Date: 2017-11 Impact factor: 3.875
Authors: Christina S Baik; Eric H Rubin; Patrick M Forde; Janice M Mehnert; Deborah Collyar; Marcus O Butler; Erica L Dixon; Laura Q M Chow Journal: Clin Cancer Res Date: 2017-09-01 Impact factor: 12.531
Authors: Daphne Day; Arta M Monjazeb; Elad Sharon; S Percy Ivy; Eric H Rubin; Gary L Rosner; Marcus O Butler Journal: Clin Cancer Res Date: 2017-09-01 Impact factor: 12.531
Authors: Tobin Strom; Louis B Harrison; Anna R Giuliano; Michael J Schell; Steven A Eschrich; Anders Berglund; William Fulp; Ram Thapa; Domenico Coppola; Sungjune Kim; Jessica Frakes; John Foekens; James J Mulé; Javier F Torres-Roca Journal: Eur J Cancer Date: 2017-08-29 Impact factor: 9.162
Authors: Valsamo Anagnostou; Mark Yarchoan; Aaron R Hansen; Hao Wang; Franco Verde; Elad Sharon; Deborah Collyar; Laura Q M Chow; Patrick M Forde Journal: Clin Cancer Res Date: 2017-09-01 Impact factor: 12.531
Authors: Jaydira Del Rivero; Lisa M Cordes; Joanna Klubo-Gwiezdzinska; Ravi A Madan; Lynnette K Nieman; James L Gulley Journal: Oncologist Date: 2019-10-10
Authors: Jordan M Thompson; Alejandro Alvarez; Monika K Singha; Matthew W Pavesic; Quy H Nguyen; Luke J Nelson; David A Fruman; Olga V Razorenova Journal: Mol Cancer Ther Date: 2018-05-02 Impact factor: 6.261