Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Jedd D. WolchokFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Vanna Chiarion‐SileniFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),René GonzálezFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Piotr RutkowskiFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Jean‐Jacques GrobFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),C. Lance CoweyFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Christopher D. LaoFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),John WagstaffCollege of Medicine, Swansea University, SwanseaDirk SchadendorfFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Pier Francesco FerrucciFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Michael SmylieFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Reinhard DummerFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Andrew HillFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),David HoggFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),John B.A.G. HaanenFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Matteo S. CarlinoFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Oliver BechterFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Michele MaioFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Iván Márquez‐RodasFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Massimo GuidoboniFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Grant A. McArthurFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Célèste LebbéFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Paolo A. AsciertoFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Georgina V. LongFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Jonathan CebonFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Jeffrey A. SosmanNorthwestern University, ChicagoMichael A. PostowFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Margaret K. CallahanFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Dana WalkerFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Linda RollinFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),Rafia BhoreFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),F. Stephen HodiFrom the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),James LarkinRoyal Marsden NHS Foundation Trust, London
2017en
ABI
Аннотация
BACKGROUND: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS: At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS: Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505 .).
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