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N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.

Collaborators (144)

Korbenfeld E, Palazzo FS, Recondo G, Chacon M, Richardet ME, Susana M, Pook D, Toner G, Gurney H, Davis I, Pittman KB, Kavina A, Schmidinger M, Loidl W, Schallier D, Machiels JP, Schoffski P, Rottey S, Dzik C, Schutz F, Franke FA, Kollmannsberger CK, Heng D, Knox J, Wood L, Basappa N, Zalewski P, Ghedira S, Miller W, Melichar B, Kubala E, Prausova J, Donskov F, Jensen NV, Geertsen P, Bono P, Ravaud A, Escudier B, Chevreau C, Rolland F, Gravis G, Tourani JM, Geoffrois L, Oudard S, Heidenreich A, Imkamp F, Bedke J, Meiler J, Retz M, Goebell P, Pahernik S, Bamias A, Papazsis K, McCaffrey JA, McDermott R, Neumann A, Berger R, Neiman V, Santoro A, Sternberg C, Roila F, Procopio G, Maio M, Bracarda S, De Giorgi U, Hongo F, Kimura G, Kanayama H, Kitamura H, Kume H, Uemura H, Yonese J, Tanabe K, Tatsugami K, Eto M, Oya M, Saito M, Uemura M, Yao M, Shinohara N, Yamaguchi R, Fukasawa S, Kato T, Sugiyama T, Obara W, Heinrich D, Straume O, Szcylik C, Slomian G, Wojcik-Tomaszewska J, Tomczak P, Zdrojowy R, Volovat C, Lungulescu D, Sinescu I, Poddubskaya E, Karlov P, Matveev V, Suarez C, Castellano D, Puente J, Arranz JA, Perez Gracia JL, Del Muro X, Jellvert A, Harmenberg U, Wagstaff J, Gore M, Nathan P, Eisen T, Alva A, Amin A, Carthon B, McDermott D, Quinn D, Vaena D, Lam E, Plimack E, Millard F, Quddus F, Beltran H, Drabkin H, Hammers HJ, Brugarolas J, Clark J, Hainsworth J, Sarantopoulos J, Sosman J, Beck JT, Fong L, Fishman M, Harrison M, Dawson N, Sharma P, Figlin R, Motzer R, George S, Srinivas S, Tykodi S, Kuzel T, Logan T, Olencki T, Vaishampayan U, Voelzke W.

Author information

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 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.).

PMID:
26406148
PMCID:
PMC5719487
DOI:
10.1056/NEJMoa1510665
[Indexed for MEDLINE]
Free PMC Article

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