Format

Send to

Choose Destination
N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma.

Collaborators (186)

Salvador Palazzo F, Zarba JJ, Gomez Bradley DM, Richardet ME, Varela MS, Recondo G, Gurney H, Pook D, Goh J, Hill AG, Davis ID, Khattak MA, De Souza P, Joshi R, Schmidinger M, Loidl W, Wolter P, Rottey S, Beuselinck B, Barrios CH, Murad A, Barros Schutz FA, Azevedo SJ, Malzyner A, Rodrigues Rosa DA, Rinck JA, Kollmannsberger CK, Miller W, Heng DYC, Bjarnason GA, Basappa NS, Sridhar S, Ghedira S, Frontera OA, Salman P, Gonzalez Mella PF, Mondaca S, Quiroga A, Gomez Wolff LR, Melichar B, Kubala E, Lakomy R, Sochor M, Donskov F, Geertsen P, Jensen NV, Bono P, Kellokumpu-Lehtinen PL, Escudier B, Barthelemy P, Ravaud A, Gravis G, Oudard S, Priou F, Chevreau C, Mouillet G, Rolland F, Grimm MO, Pahernik SA, Hadaschik B, Zengerling F, Gruenwald V, Herrmann E, Retz M, Goebell PJ, Bergmann L, Von Amsberg G, Ohlmann C, Schostak M, Schnoeller T, van Essen J, Kocsis J, Piko B, Mangel L, Geczi L, McDermott R, McCaffrey JA, Neiman V, Leibowitz-Amit R, Keizman D, Peer A, Sella A, Porta C, Bracarda S, Procopio G, Basso U, Carteni G, De Giorgi U, Tomita Y, Kondo T, Kimura G, Inoue T, Wakumoto Y, Yao M, Fujii Y, Obara W, Oya M, Tsuchiya K, Kojima T, Harada K, Kato T, Sugiyama T, Takahashi M, Uemura M, Ebara S, Fukasawa S, Kawano Y, Kobayashi K, Ohyama C, Tatsugami K, Uemura H, Kume H, Hongo F, Takahashi S, Takamoto A, Tohru N, Lee JL, Rha SY, Lopez Chuken YA, Rodriguez Cid J, Dominguez Andrade A, Hernandez CA, Oosting SJ, Haanen J, Van Herpen C, Ziobro M, Zdrojowy R, Tomczak P, Castellano D, Grande E, Maroto P, Duran I, Suarez C, Esteban E, Puente J, Harmenberg U, Liu JH, Chang WC, Erman M, Senol Coskun H, Dane F, Powles T, Hawkins R, Nathan P, Gore M, Wagstaff J, Venugopal B, Motzer RJ, Hammers HJ, Tannir NM, Sharma P, McDermott DF, Plimack ER, George S, Choueiri TK, Rini B, Tykodi S, Amin A, Harrison MR, Srinivas S, Redman BS, Carthon B, Gao J, Carducci M, Kluger HM, Hutson TE, Vaena D, Zakharia Y, Olencki T, Pal S, Dawson N, Fishman MN, Infante JR, Nair SG, Drabkin H, Logan T, Appleman L, Figlin RA, Brugarolas J, Ryan CW, Mannuel HD, Quinn D, Randall JM, Williamson SK, Vaishampayan UN, Graham RM.

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; University of Texas M.D. Anderson Cancer Center, Houston (N.M.T., P. Sharma); Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center (D.F.M.), and Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School (T.K.C.), Boston; Centro Internacional de Estudios Clínicos (O.A.F.) and Fundación Arturo López Pérez (P. Salman), Santiago, Chile; Palacký University and University Hospital Olomouc, Olomouc, Czech Republic (B.M.); Fox Chase Cancer Center, Philadelphia (E.R.P.); Hôpitaux Universitaires de Strasbourg, Strasbourg (P.B.), Bordeaux University Hospital, Hôpital Saint-André, Bordeaux (A.R.), and Institut Gustave Roussy, Villejuif (B.E.) - all in France; Istituto di Ricovero e Cura a Carattere Scientifico San Matteo University Hospital Foundation, Pavia (C.P.), and Ospedale San Donato, Azienda Unità Sanitaria Locale Toscana Sud-Est, Istituto Toscano Tumori, Arezzo (S.B.) - both in Italy; Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust (T.P.), and Cancer Research UK (R.H.), London; Aarhus University Hospital, Aarhus, Denmark (F.D.); Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, and Tel Aviv University, Tel Aviv - both in Israel (V.N.); British Columbia Cancer Agency, Vancouver, Canada (C.K.K.); Westmead Hospital and Macquarie University, Sydney (H.G.); Jena University Hospital, Jena, Germany (M.-O.G.); Centro de Pesquisa em Oncologia, Hospital São Lucas, Porto Alegre, Brazil (C.H.B.); Niigata University, Niigata, Japan (Y.T.); Hospital Universitario 12 de Octubre, Madrid (D.C.); Cleveland Clinic Taussig Cancer Institute, Cleveland (B.I.R.); Bristol-Myers Squibb, Princeton, NJ (A.C.C., S.M., M.B.M., M.W.-R., J.D.); and Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore (H.J.H.).

Abstract

BACKGROUND:

Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.

METHODS:

We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk.

RESULTS:

A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P=0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46%) and 335 patients (63%), respectively. Treatment-related adverse events leading to discontinuation occurred in 22% and 12% of the patients in the respective groups.

CONCLUSIONS:

Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 214 ClinicalTrials.gov number, NCT02231749 .).

PMID:
29562145
PMCID:
PMC5972549
DOI:
10.1056/NEJMoa1712126
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center