Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma

被引：184

作者：

Blank, Christian U. ^{[1
,9
,24
]}

Lucas, Minke W. ^{[1
]}

Scolyer, Richard A. ^{[25
,26
,27
,28
,30
]}

van de Wiel, Bart A.

Menzies, Alexander M. ^{[25
,26
,31
]}

Lopez-Yurda, Marta ^{[2
,3
]}

Hoeijmakers, Lotte L. ^{[1
]}

Saw, Robyn P. M. ^{[25
,26
,29
]}

Lijnsvelt, Judith M. ^{[1
]}

Maher, Nigel G. ^{[25
,26
]}

Pulleman, Saskia M. ^{[1
]}

Gonzalez, Maria ^{[25
,26
]}

Acosta, Alejandro Torres ^{[2
,3
]}

van Houdt, Winan J. ^{[4
]}

Lo, Serigne N. ^{[25
,26
]}

Kuijpers, Anke M. J. ^{[4
]}

Spillane, Andrew ^{[25
,26
,32
,33
]}

Klop, W. Martin C. ^{[5
]}

Pennington, Thomas E. ^{[25
,26
,29
]}

Zuur, Charlotte L. ^{[5
,10
]}

Shannon, Kerwin F. ^{[25
,26
,29
]}

Seinstra, Beatrijs A. ^{[6
]}

Rawson, Robert V. ^{[25
,26
,28
,30
]}

Haanen, John B. A. G. ^{[1
,7
,9
,46
]}

Ch'ng, Sydney ^{[25
,26
,29
]}

Naipal, Kishan A. T. ^{[1
,11
]}

Stretch, Jonathan ^{[25
,26
,29
]}

van Thienen, Johannes V. ^{[1
]}

Rtshiladze, Michael A. ^{[25
,26
,29
]}

Wilgenhof, Sofie ^{[1
]}

Kapoor, Rony ^{[33
]}

Meerveld-Eggink, Aafke ^{[1
]}

Grijpink-Ongering, Lindsay G. ^{[2
,3
]}

van Akkooi, Alexander C. J. ^{[4
,25
,26
,29
,34
]}

Reijers, Irene L. M. ^{[1
]}

Gyorki, David E. ^{[35
,36
]}

Gruenhagen, Dirk J. ^{[12
]}

Speetjens, Frank M. ^{[9
]}

Vliek, Sonja B. ^{[14
]}

Placzke, Joanna ^{[47
]}

Spain, Lavinia ^{[37
]}

Stassen, Robert C. ^{[11
,12
]}

Amini-Adle, Mona ^{[48
]}

Lebbe, Celeste ^{[49
]}

Faries, Mark B. ^{[52
]}

Robert, Caroline ^{[50
,51
]}

Ascierto, Paolo A. ^{[53
]}

van Rijn, Rozemarijn ^{[15
]}

van den Berkmortel, Franchette W. P. J. ^{[16
]}

Piersma, Djura ^{[17
]}

机构：

[1] Netherlands Canc Inst, Dept Med Oncol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[2] Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands

[3] Netherlands Canc Inst, Dept Biometr, Amsterdam, Netherlands

[4] Netherlands Canc Inst, Dept Surg Oncol, Amsterdam, Netherlands

[5] Netherlands Canc Inst, Dept Head & Neck Surg, Amsterdam, Netherlands

[6] Netherlands Canc Inst, Dept Radiol, Amsterdam, Netherlands

[7] Netherlands Canc Inst, Dept Mol Oncol & Immunol, Amsterdam, Netherlands

[8] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, Amsterdam, Netherlands

[9] Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands

[10] Leiden Univ, Med Ctr, Dept Otorhinolaryngol Head & Neck Surger, Leiden, Netherlands

[11] Erasmus MC, Dept Med Oncol, Rotterdam, Netherlands

[12] Erasmus MC, Dept Surg Oncol, Rotterdam, Netherlands

[13] Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands

[14] Univ Utrecht, Univ Med Ctr Utrecht, Dept Med Oncol, Utrecht, Netherlands

[15] Med Ctr Leeuwarden, Dept Med Oncol, Leeuwarden, Netherlands

[16] Zuyderland Med Ctr, Dept Med Oncol, Geleen, Netherlands

[17] Med Spectrum Twente, Dept Med Oncol, Enschede, Netherlands

[18] Maxima Med Ctr, Dept Med Oncol, Veldhoven, Netherlands

[19] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Med Oncol, Med Ctr, Maastricht, Netherlands

[20] Amphia Hosp, Dept Med Oncol, Breda, Netherlands

[21] Radboud Univ Nijmegen, Dept Med Oncol, Med Ctr, Nijmegen, Netherlands

[22] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands

[23] Isala Hosp, Isala Oncol Ctr, Zwolle, Netherlands

[24] Univ Clin Regensburg, Dept Hematol & Med Oncol, Regensburg, Germany

[25] Univ Sydney, Melanoma Inst Australia, Sydney, Australia

[26] Univ Sydney, Fac Med & Hlth, Sydney, Australia

[27] Univ Sydney, Charles Perkins Ctr, Sydney, Australia

[28] Royal Prince Alfred Hosp, Dept Tissue Pathol & Diagnost Oncol, Camperdown, Australia

[29] Royal Prince Alfred Hosp, Dept Melanoma & Surg Oncol, Sydney, Australia

[30] NSW Hlth Pathol, Sydney, Australia

[31] Royal North Shore & Mater Hosp, Dept Med Oncol, Sydney, Australia

[32] Royal North Shore & Mater Hosp, Dept Breast & Melanoma Surg, Sydney, Australia

[33] Mater Hosp, Dept Radiol, Sydney, Australia

[34] Royal Prince Alfred Hosp, Inst Acad Surg, Camperdown, NSW, Australia

[35] Peter MacCallum Canc Ctr, Div Canc Surg, Melbourne, Vic, Australia

[36] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[37] Peter MacCallum Canc Ctr, Dept Med Oncol, East Melbourne, Australia

[38] Lake Macquarie Private Hosp, Lake Macquarie Oncol, Newcastle, NSW, Australia

[39] Calvary Mater Hosp, Dept Med Oncol, Newcastle, NSW, Australia

[40] Univ Newcastle, Sch Med & Publ Hlth, Dept Med, Newcastle, NSW, Australia

[41] Univ Queensland, Princess Alexandra Hosp, Dept Med Oncol, Brisbane, Australia

[42] Fiona Stanley Hosp, Dept Med Oncol, Perth, WA, Australia

[43] Alfred Hlth, Dept Med Oncol, Melbourne, Vic, Australia

[44] Monash Univ, Sch Translat Med, Dept Med, Melbourne, Vic, Australia

[45] Westmead Hosp & Blacktown, Dept Med Oncol, Sydney, Australia

[46] CHU Vaudois, Melanoma Clin, Lausanne, Switzerland

[47] Maria Sklodowska Curie Natl Res Inst Oncol, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland

[48] Ctr Leon Berard, Dept Med Oncol, Lyon, France

[49] Univ Paris Cite, St Louis Hosp, Assistance Publ Hop Paris AP HP, Canc Inst AP HP,Dermatooncol & Clin Invest Ctr, Paris, France

[50] Gustave Roussy, Dept Med Oncol, Villejuif, France

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2024年

基金：

英国医学研究理事会;

关键词：

ADJUVANT NIVOLUMAB; DOUBLE-BLIND; IV MELANOMA; OPACIN-NEO; SURVIVAL; IMMUNOTHERAPY; EFFICACY;

D O I：

10.1056/NEJMoa2402604

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Phase 1-2 trials involving patients with resectable, macroscopic stage III melanoma have shown that neoadjuvant immunotherapy is more efficacious than adjuvant immunotherapy. Methods In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma, in a 1:1 ratio, to receive two cycles of neoadjuvant ipilimumab plus nivolumab and then undergo surgery or to undergo surgery and then receive 12 cycles of adjuvant nivolumab. Only the patients in the neoadjuvant group who had a partial response or nonresponse received subsequent adjuvant treatment. The primary end point was event-free survival. Results A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of the patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% among patients in the neoadjuvant group who had a major pathological response, 76.1% among those who had a partial response, and 57.0% among those who had a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of the patients in the neoadjuvant group and in 14.7% in the adjuvant group. Conclusions Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.)

引用

页数：13

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