Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Christopher D Lao, C Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Pier F Ferrucci, Michael Smylie, David Hogg, Andrew Hill, Ivan Márquez-Rodas, John Haanen, Massimo Guidoboni, Michele Maio, Patrick Schöffski, Matteo S CarlinoCéleste Lebbé, Grant McArthur, Paolo A Ascierto, Gregory A Daniels, Georgina V Long, Lars Bastholt, Jasmine I Rizzo, Agnes Balogh, Andriy Moshyk, F Stephen Hodi, Jedd D Wolchok

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.

METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.

RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 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, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.

CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

Original languageEnglish
Pages (from-to)1535-1546
Number of pages12
JournalThe New England journal of medicine
Volume381
Issue number16
DOIs
Publication statusPublished - Oct 17 2019

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Melanoma
Survival
ipilimumab
nivolumab
Disease-Free Survival
Placebos
Quality of Life
Poisons

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Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J-J., Rutkowski, P., Lao, C. D., ... Wolchok, J. D. (2019). Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. The New England journal of medicine, 381(16), 1535-1546. https://doi.org/10.1056/NEJMoa1910836

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. / Larkin, James; Chiarion-Sileni, Vanna; Gonzalez, Rene; Grob, Jean-Jacques; Rutkowski, Piotr; Lao, Christopher D; Cowey, C Lance; Schadendorf, Dirk; Wagstaff, John; Dummer, Reinhard; Ferrucci, Pier F; Smylie, Michael; Hogg, David; Hill, Andrew; Márquez-Rodas, Ivan; Haanen, John; Guidoboni, Massimo; Maio, Michele; Schöffski, Patrick; Carlino, Matteo S; Lebbé, Céleste; McArthur, Grant; Ascierto, Paolo A; Daniels, Gregory A; Long, Georgina V; Bastholt, Lars; Rizzo, Jasmine I; Balogh, Agnes; Moshyk, Andriy; Hodi, F Stephen; Wolchok, Jedd D.

In: The New England journal of medicine, Vol. 381, No. 16, 17.10.2019, p. 1535-1546.

Research output: Contribution to journalArticle

Larkin, J, Chiarion-Sileni, V, Gonzalez, R, Grob, J-J, Rutkowski, P, Lao, CD, Cowey, CL, Schadendorf, D, Wagstaff, J, Dummer, R, Ferrucci, PF, Smylie, M, Hogg, D, Hill, A, Márquez-Rodas, I, Haanen, J, Guidoboni, M, Maio, M, Schöffski, P, Carlino, MS, Lebbé, C, McArthur, G, Ascierto, PA, Daniels, GA, Long, GV, Bastholt, L, Rizzo, JI, Balogh, A, Moshyk, A, Hodi, FS & Wolchok, JD 2019, 'Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma', The New England journal of medicine, vol. 381, no. 16, pp. 1535-1546. https://doi.org/10.1056/NEJMoa1910836
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J-J, Rutkowski P, Lao CD et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. The New England journal of medicine. 2019 Oct 17;381(16):1535-1546. https://doi.org/10.1056/NEJMoa1910836
Larkin, James ; Chiarion-Sileni, Vanna ; Gonzalez, Rene ; Grob, Jean-Jacques ; Rutkowski, Piotr ; Lao, Christopher D ; Cowey, C Lance ; Schadendorf, Dirk ; Wagstaff, John ; Dummer, Reinhard ; Ferrucci, Pier F ; Smylie, Michael ; Hogg, David ; Hill, Andrew ; Márquez-Rodas, Ivan ; Haanen, John ; Guidoboni, Massimo ; Maio, Michele ; Schöffski, Patrick ; Carlino, Matteo S ; Lebbé, Céleste ; McArthur, Grant ; Ascierto, Paolo A ; Daniels, Gregory A ; Long, Georgina V ; Bastholt, Lars ; Rizzo, Jasmine I ; Balogh, Agnes ; Moshyk, Andriy ; Hodi, F Stephen ; Wolchok, Jedd D. / Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. In: The New England journal of medicine. 2019 ; Vol. 381, No. 16. pp. 1535-1546.
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abstract = "BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 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, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52{\%} in the nivolumab-plus-ipilimumab group and 44{\%} in the nivolumab group, as compared with 26{\%} in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).",
author = "James Larkin and Vanna Chiarion-Sileni and Rene Gonzalez and Jean-Jacques Grob and Piotr Rutkowski and Lao, {Christopher D} and Cowey, {C Lance} and Dirk Schadendorf and John Wagstaff and Reinhard Dummer and Ferrucci, {Pier F} and Michael Smylie and David Hogg and Andrew Hill and Ivan M{\'a}rquez-Rodas and John Haanen and Massimo Guidoboni and Michele Maio and Patrick Sch{\"o}ffski and Carlino, {Matteo S} and C{\'e}leste Lebb{\'e} and Grant McArthur and Ascierto, {Paolo A} and Daniels, {Gregory A} and Long, {Georgina V} and Lars Bastholt and Rizzo, {Jasmine I} and Agnes Balogh and Andriy Moshyk and Hodi, {F Stephen} and Wolchok, {Jedd D}",
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T1 - Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

AU - Larkin, James

AU - Chiarion-Sileni, Vanna

AU - Gonzalez, Rene

AU - Grob, Jean-Jacques

AU - Rutkowski, Piotr

AU - Lao, Christopher D

AU - Cowey, C Lance

AU - Schadendorf, Dirk

AU - Wagstaff, John

AU - Dummer, Reinhard

AU - Ferrucci, Pier F

AU - Smylie, Michael

AU - Hogg, David

AU - Hill, Andrew

AU - Márquez-Rodas, Ivan

AU - Haanen, John

AU - Guidoboni, Massimo

AU - Maio, Michele

AU - Schöffski, Patrick

AU - Carlino, Matteo S

AU - Lebbé, Céleste

AU - McArthur, Grant

AU - Ascierto, Paolo A

AU - Daniels, Gregory A

AU - Long, Georgina V

AU - Bastholt, Lars

AU - Rizzo, Jasmine I

AU - Balogh, Agnes

AU - Moshyk, Andriy

AU - Hodi, F Stephen

AU - Wolchok, Jedd D

N1 - Copyright © 2019 Massachusetts Medical Society.

PY - 2019/10/17

Y1 - 2019/10/17

N2 - BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 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, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

AB - BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 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, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

U2 - 10.1056/NEJMoa1910836

DO - 10.1056/NEJMoa1910836

M3 - Article

C2 - 31562797

VL - 381

SP - 1535

EP - 1546

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 16

ER -