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

被引：2752

作者：

Larkin, J. ^{[1
]}

Chiarion-Sileni, V. ^{[3
]}

Gonzalez, R. ^{[8
]}

Grob, J-J ^{[9
]}

Rutkowski, P. ^{[12
]}

Lao, C. D. ^{[13
]}

Cowey, C. L. ^{[14
]}

Schadendorf, D. ^{[15
,16
]}

Wagstaff, J. ^{[2
]}

Dummer, R. ^{[17
]}

Ferrucci, P. F. ^{[4
]}

Smylie, M. ^{[18
]}

Hogg, D. ^{[19
]}

Hill, A. ^{[20
]}

Marquez-Rodas, I. ^{[24
,25
]}

Haanen, J. ^{[26
]}

Guidoboni, M. ^{[6
]}

Maio, M. ^{[7
]}

Schoffski, P. ^{[27
]}

Carlino, M. S. ^{[21
]}

Lebbe, C. ^{[10
,11
]}

McArthur, G. ^{[23
]}

Ascierto, P. A. ^{[5
]}

Daniels, G. A. ^{[28
]}

Long, G. V. ^{[21
,22
]}

Bastholt, L. ^{[29
]}

Rizzo, J. I. ^{[30
]}

Balogh, A. ^{[30
]}

Moshyk, A. ^{[30
]}

Hodi, F. S. ^{[31
]}

Wolchok, J. D. ^{[32
,33
]}

机构：

[1] Royal Marsden NHS Fdn Trust, 203 Fulham Rd, London SW3 6JJ, England

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

[3] IRCCS, Oncol Inst Veneto, Padua, Italy

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

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

[6] IRCCS Ist Sci Romagnolo Studio Cura Tumori, Immunotherapy & Somat Cell Therapy Unit, Meldola, Italy

[7] Univ Hosp, Ctr Immunooncol Med Oncol & Immunotherapy, Siena, Italy

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

[9] Aix Marseille Univ, Hop Timone, AP HM, Marseille, France

[10] Univ Paris, AP HP, INSERM, Dermatol,Unite 976, Paris, France

[11] St Louis Hosp, Ctr Invest Clin, Paris, France

[12] Maria Sklodowska Curie Inst, Oncol Ctr, Warsaw, Poland

[13] Univ Michigan, Ann Arbor, MI 48109 USA

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

[15] Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany

[16] German Canc Consortium, Heidelberg, Germany

[17] Univ Spital, Zurich, Switzerland

[18] Cross Canc Inst, Edmonton, AB, Canada

[19] Princess Margaret Canc Ctr, Toronto, ON, Canada

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

[21] Univ Sydney, Melanoma Inst Australia, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia

[22] Royal North Shore & Mater Hosp, Sydney, NSW, Australia

[23] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

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

[25] Ctr Invest Biomed Red Oncol, Madrid, Spain

[26] Netherlands Canc Inst, Amsterdam, Netherlands

[27] Univ Hosp Leuven, Dept Gen Med Oncol, Leuven Canc Inst, Leuven, Belgium

[28] Univ Calif San Diego, Hlth La Jolla Moores, La Jolla, CA 92093 USA

[29] Odense Univ Hosp, Dept Oncol, Odense, Denmark

[30] Bristol Myers Squibb, Princeton, NJ USA

[31] Dana Farber Canc Inst, Boston, MA 02115 USA

[32] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[33] Weill Cornell Med Coll, New York, NY USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2019年 / 381卷 / 16期

关键词：

D O I：

10.1056/NEJMoa1910836

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1535 / 1546

页数：12

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