Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

被引：1065

作者：

Eggermont, A. M. M. ^{[1
]}

Chiarion-Sileni, V. ^{[6
]}

Grob, J. -J. ^{[2
]}

Dummer, R. ^{[11
]}

Wolchok, J. D. ^{[12
]}

Schmidt, H. ^{[13
]}

Hamid, O. ^{[15
]}

Robert, C. ^{[1
]}

Ascierto, P. A. ^{[7
]}

Richards, J. M. ^{[16
]}

Lebbe, C. ^{[3
]}

Ferraresi, V. ^{[8
]}

Smylie, M. ^{[17
]}

Weber, J. S. ^{[18
]}

Maio, M. ^{[9
]}

Bastholt, L. ^{[14
]}

Mortier, L. ^{[4
]}

Thomas, L. ^{[5
]}

Tahir, S. ^{[19
]}

Hauschild, A. ^{[20
]}

Hassel, J. C. ^{[21
]}

Hodi, F. S. ^{[22
]}

Taitt, C. ^{[23
]}

de Pril, V. ^{[23
]}

de Schaetzen, G. ^{[24
]}

Suciu, S. ^{[24
]}

Testori, A. ^{[10
]}

机构：

[1] Gustave Roussy Canc Campus Grand Paris, 114 Rue Edouard Vaillant, F-94805 Villejuif, France

[2] Aix Marseille Univ, Hop La Timone, Marseille, France

[3] Hop St Louis, AP HP, Paris, France

[4] Univ Lille, Ctr Hosp Univ Lille, INSERM, Unite 1189,Serv Dermatol, Lille, France

[5] CHU Lyon, Lyon, France

[6] Oncol Inst Veneto, Ist Ricovero & Cura Carattere Sci, Padua, Italy

[7] Fdn G Pascale, Ist Nazl Tumori, Naples, Italy

[8] Ist Fisioterap Ospitalieri, Rome, Italy

[9] Univ Hosp Siena, Ist Toscano Tumori, Siena, Italy

[10] European Inst Oncol, Milan, Italy

[11] Univ Zurich Hosp, Zurich, Switzerland

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

[13] Aarhus Univ Hosp, Aarhus, Denmark

[14] Odense Univ Hosp, Odense, Denmark

[15] Angeles Clin & Res Inst, Los Angeles, CA USA

[16] Oncol Specialists, Park Ridge, IL USA

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

[18] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[19] Broomfield Hosp, Chelmsford, England

[20] Univ Klinikum Schleswig Holstein, Kiel, Germany

[21] Univ Heidelberg Hosp, Heidelberg, Germany

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

[23] Bristol Myers Squibb Co, Princeton, NJ USA

[24] European Org Res Treatment Canc, Brussels, Belgium

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2016年 / 375卷 / 19期

关键词：

NODE-POSITIVE MELANOMA; HIGH-RISK MELANOMA; CUTANEOUS MELANOMA; INTERFERON-ALPHA; TUMOR BURDEN; MULTICENTER; ULCERATION;

D O I：

10.1056/NEJMoa1611299

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. METHODS After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety. RESULTS At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immunerelated adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events. CONCLUSIONS As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo.

引用

页码：1845 / 1855

页数：11

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