Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma

被引：120

作者：

Wolchok, Jedd D. ^{[1
,2
]}

Chiarion-Sileni, Vanna ^{[4
]}

Rutkowski, Piotr ^{[10
]}

Cowey, C. Lance ^{[11
]}

Schadendorf, Dirk ^{[12
,13
,14
,15
,16
]}

Wagstaff, John ^{[17
,22
]}

Queirolo, Paola ^{[5
]}

Dummer, Reinhard ^{[20
]}

Butler, Marcus O. ^{[21
]}

Hill, Andrew G. ^{[23
]}

Postow, Michael A. ^{[2
,3
]}

Gaudy-Marqueste, Caroline ^{[30
]}

Medina, Theresa ^{[34
]}

Lao, Christopher D. ^{[35
]}

Walker, John

Marquez-Rodas, Ivan ^{[36
]}

Haanen, John B. A. G. ^{[37
]}

Guidoboni, Massimo ^{[6
]}

Maio, Michele ^{[7
,8
]}

Schoeffski, Patrick ^{[38
,39
]}

Carlino, Matteo S. ^{[24
,25
,26
]}

Sandhu, Shahneen ^{[29
]}

Lebbe, Celeste ^{[31
,32
,33
]}

Ascierto, Paolo A. ^{[9
]}

Long, Georgina V. ^{[26
,27
,28
]}

Ritchings, Corey ^{[40
]}

Nassar, Ayman ^{[18
]}

Askelson, Margarita ^{[40
]}

Benito, Melanie Pe ^{[40
]}

Wang, Wenjia ^{[40
]}

Hodi, F. Stephen ^{[41
]}

Larkin, James ^{[19
]}

机构：

[1] Weill Cornell Med, Sandra & Edward Meyer Canc Ctr, 413 E 69th St,Belfer Res Bldg,BRB-1302, New York, NY 10021 USA

[2] Weill Cornell Med, Dept Med, New York, NY USA

[3] Mem Sloan Kettering Canc Ctr, New York, NY USA

[4] IRCCS, Ist Oncol Veneto, Padua, Italy

[5] IRCCS, European Inst Oncol, Milan, Italy

[6] IRCCS, Ist Sci Romagnolo Studio & Cura Tumori, Meldola, Italy

[7] Univ Siena, Siena, Italy

[8] Univ Hosp Siena, Ctr Immunooncol, Siena, Italy

[9] Ist Nazl Tumori IRCCS Fdn Pascale, Naples, Italy

[10] Maria Sklodowska Curie Natl Inst Oncol, Warsaw, Poland

[11] Baylor Charles A Sammons Canc Ctr, Texas Oncol, Dallas, TX USA

[12] Univ Hosp Essen, Essen, Germany

[13] German Canc Consortium, Essen, Germany

[14] Natl Ctr Tumor Dis West, Essen, Germany

[15] Res Alliance Ruhr, Res Ctr One Hlth, Essen, Germany

[16] Univ Duisburg Essen, Essen, Germany

[17] Swansea Univ, Coll Med, Swansea, W Glam, Wales

[18] Bristol Myers Squibb, Uxbridge, Middx, England

[19] Royal Marsden Hosp, London, England

[20] Univ Zurich, Dept Dermatol, Zurich, Switzerland

[21] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[22] Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada

[23] Tasman Oncol Res, Southport, Qld, Australia

[24] Westmead Hosp, Westmead, NSW, Australia

[25] Blacktown Hosp, Blacktown, NSW, Australia

[26] Univ Sydney, Melanoma Inst Australia, Sydney, NSW, Australia

[27] Royal North Shore Hosp, Sydney, NSW, Australia

[28] Mater Hosp, Sydney, NSW, Australia

[29] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[30] Aix Marseille Univ, Assistance Publ Hop Marseille, Marseille, France

[31] Univ Paris Cite, AP HP, Dermatooncol, Clin Invest Ctr, Paris, France

[32] AP HP Nord Paris Cite, Inst Canc, INSERM, Unite 976, Paris, France

[33] St Louis Hosp, Paris, France

[34] Univ Colorado, Ctr Canc, Aurora, CO USA

[35] Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI USA

[36] Hosp Gen Univ Gregorio Maranon, Madrid, Spain

[37] Netherlands Canc Inst, Amsterdam, Netherlands

[38] Katholieke Univ Leuven, Univ Hosp Leuven, Leuven, Belgium

[39] Katholieke Univ Leuven, Leuven Canc Inst, Leuven, Belgium

[40] Bristol Myers Squibb, Princeton, NJ USA

[41] Dana Farber Canc Inst, Boston, MA USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2025年 / 392卷 / 01期

关键词：

SURVIVAL; RELATLIMAB; NIVO; IPI;

D O I：

10.1056/NEJMoa2407417

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions. METHODS We randomly assigned patients with previously untreated advanced melanoma, in a 1:1:1 ratio, to one of the following regimens: nivolumab (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 placebo; or ipilimumab (3 mg per kilogram) every 3 weeks for four doses plus placebo. Treatment was continued until the occurrence of disease progression, unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to BRAF mutation status, metastasis stage, and programmed death ligand 1 expression. Here, we report the final, 10-year results of this trial, including results for overall survival and melanoma-specific survival, as well as durability of response. RESULTS With a minimum follow-up of 10 years, median overall survival was 71.9 months with nivolumab plus ipilimumab, 36.9 months with nivolumab, and 19.9 months with ipilimumab. The hazard ratio for death was 0.53 (95% confidence interval [CI], 0.44 to 0.65) for nivolumab plus ipilimumab as compared with ipilimumab and was 0.63 (95% CI, 0.52 to 0.76) for nivolumab as compared with ipilimumab. Median melanoma-specific survival was more than 120 months with nivolumab plus ipilimumab (not reached, with 37% of the patients alive at the end of the trial), 49.4 months with nivolumab, and 21.9 months with ipilimumab. Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97% with nivolumab, and 88% with ipilimumab. CONCLUSIONS The final trial results showed a continued, ongoing survival benefit with nivolumab plus ipilimumab and with nivolumab monotherapy, as compared with ipilimumab monotherapy, in patients with advanced melanoma.

引用

页码：11 / 22

页数：12

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