Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma

被引：0

作者：

Blank, Christian U. ^{[1
,2
,10
,25
]}

Lucas, Minke W. ^{[1
,2
]}

Scolyer, Richard A. ^{[26
,27
,28
,29
,31
]}

van de Wiel, Bart A. ^{[3
]}

Menzies, Alexander M. ^{[26
,27
,32
]}

Lopez-Yurda, Marta ^{[4
]}

Hoeijmakers, Lotte L. ^{[1
,2
]}

Saw, Robyn P. M. ^{[26
,27
,30
]}

Lijnsvelt, Judith M. ^{[1
,2
]}

Maher, Nigel G. ^{[26
,27
]}

Pulleman, Saskia M. ^{[1
,2
]}

Gonzalez, Maria ^{[26
]}

Torres Acosta, Alejandro ^{[4
]}

van Houdt, Winan J. ^{[5
]}

Lo, Serigne N. ^{[26
,27
]}

Kuijpers, Anke M. J. ^{[5
]}

Spillane, Andrew ^{[26
,27
,33
]}

Klop, W. Martin C. ^{[6
]}

Pennington, Thomas E. ^{[26
,27
,30
]}

Zuur, Charlotte L. ^{[6
,11
]}

Shannon, Kerwin F. ^{[26
,27
,30
]}

Seinstra, Beatrijs A. ^{[7
]}

Rawson, Robert V. ^{[26
,29
,31
]}

Haanen, John B. A. G. ^{[1
,2
,8
,10
,47
]}

Ch'ng, Sydney ^{[26
,27
,30
]}

Naipal, Kishan A. T. ^{[1
,2
,12
]}

Stretch, Jonathan ^{[26
,27
,30
]}

van Thienen, Johannes V. ^{[1
,2
]}

Rtshiladze, Michael A. ^{[26
,27
,30
]}

Wilgenhof, Sofie ^{[1
,2
]}

Kapoor, Rony ^{[34
]}

Meerveld-Eggink, Aafke ^{[1
,2
]}

Grijpink-Ongering, Lindsay G. ^{[4
]}

van Akkooi, Alexander C. J. ^{[5
,26
,27
,30
,35
]}

Reijers, Irene L. M. ^{[1
,2
]}

Gyorki, David E. ^{[36
,37
]}

Gruenhagen, Dirk J. ^{[13
]}

Speetjens, Frank M. ^{[10
]}

Vliek, Sonja B. ^{[15
]}

Placzke, Joanna ^{[48
]}

Spain, Lavinia ^{[38
]}

Stassen, Robert C. ^{[12
,13
]}

Amini-Adle, Mona ^{[49
]}

Lebbe, Celeste ^{[50
]}

Faries, Mark B. ^{[53
]}

Robert, Caroline ^{[51
,52
]}

Ascierto, Paolo A. ^{[54
]}

van Rijn, Rozemarijn ^{[16
]}

van den Berkmortel, Franchette W. P. J. ^{[17
]}

Piersma, Djura ^{[18
]}

机构：

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

[2] Netherlands Canc Inst, Div Mol Oncol & Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

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

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

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

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

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

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

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

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

[11] Leiden Univ, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Leiden, Netherlands

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

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

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

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

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

[17] Zuyderland Med Ctr, Dept Med Oncol, Sittard Geleen, Netherlands

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

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

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

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

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

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

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

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

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

[27] Univ Sydney, Fac Med & Hlth, Sydney, NSW, Australia

[28] Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia

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

[30] Royal Prince Alfred Hosp, Dept Melanoma & Surg Oncol, Camperdown, NSW, Australia

[31] NSW Hlth Pathol, Sydney, NSW, Australia

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

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

[34] Mater Hosp, Dept Radiol, Sydney, NSW, Australia

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

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

[37] Univ Melbourne, Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

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

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

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

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

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

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

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

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

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

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

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

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

[50] St Louis Hosp, AP HP, Univ Paris Cite,INSERM,Unite 976, Dermatooncol & Clin Invest Ctr,Canc Inst,Nord Par, Paris, France

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2024年 / 391卷 / 18期

关键词：

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

D O I：

暂无

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND In phase 1-2 trials in patients with resectable, macroscopic stage III melanoma, neoadjuvant immunotherapy was more efficacious than adjuvant immunotherapy. METHODS In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab. Only patients in the neoadjuvant group with a partial response or nonresponse received 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 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% in patients in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of 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.

引用

页码：1696 / 1708

页数：13

共 50 条

[31] Real World Outcomes of Ipilimumab and Nivolumab in Patients with Metastatic Melanoma [J].

Asher, Nethanel ;

Ben-Betzalel, Guy ;

Lev-Ari, Shaked ;

Shapira-Frommer, Ronnie ;

Steinberg-Silman, Yael ;

Gochman, Neta ;

Schachter, Jacob ;

Meirson, Tomer ;

Markel, Gal .

CANCERS, 2020, 12 (08) :1-18

[32] Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma [J].

Larkin, J. ;

Chiarion-Sileni, V. ;

Gonzalez, R. ;

Grob, J. J. ;

Cowey, C. L. ;

Lao, C. D. ;

Schadendorf, D. ;

Dummer, R. ;

Smylie, M. ;

Rutkowski, P. ;

Ferrucci, P. F. ;

Hill, A. ;

Wagstaff, J. ;

Carlino, M. S. ;

Haanen, J. B. ;

Maio, M. ;

Marquez-Rodas, I. ;

McArthur, G. A. ;

Ascierto, P. A. ;

Long, G. V. ;

Callahan, M. K. ;

Postow, M. A. ;

Grossmann, K. ;

Sznol, M. ;

Dreno, B. ;

Bastholt, L. ;

Yang, A. ;

Rollin, L. M. ;

Horak, C. ;

Hodi, F. S. ;

Wolchok, J. D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (01) :23-34

[33] Nivolumab plus ipilimumab in the treatment of advanced melanoma [J].

Tsai, Katy K. ;

Daud, Adil I. .

JOURNAL OF HEMATOLOGY & ONCOLOGY, 2015, 8

[34] Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain [J].

Tawbi, Hussein A. ;

Forsyth, Peter A. ;

Algazi, Alain ;

Hamid, Omid ;

Hodi, F. Stephen ;

Moschos, Stergios J. ;

Khushalani, Nikhil I. ;

Lewis, Karl ;

Lao, Christopher D. ;

Postow, Michael A. ;

Atkins, Michael B. ;

Ernstoff, Marc S. ;

Reardon, David A. ;

Puzanov, Igor ;

Kudchadkar, Ragini R. ;

Thomas, Reena P. ;

Tarhini, Ahmad ;

Pavlick, Anna C. ;

Jiang, Joel ;

Avila, Alexandre ;

Demelo, Sheena ;

Margolin, Kim .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (08) :722-730

[35] Nivolumab plus ipilimumab in the treatment of advanced melanoma [J].

Katy K. Tsai ;

Adil I. Daud .

Journal of Hematology & Oncology, 8

[36] Molecular and Clinicopathological Biomarkers in the Neoadjuvant Treatment of Patients with Advanced Resectable Melanoma [J].

Blonski, Piotr J. ;

Czarnecka, Anna M. ;

Ostaszewski, Krzysztof ;

Szumera-Cieckiewicz, Anna ;

Rutkowski, Piotr .

BIOMEDICINES, 2024, 12 (03)

[37] Neoadjuvant ipilimumab plus nivolumab therapy as a potential organ preservation strategy in mucosal melanoma: case report [J].

Ong, Claire ;

Samlowski, Wolfram .

FRONTIERS IN ONCOLOGY, 2024, 14

[38] Adjuvant ipilimumab in stage III melanoma: New landscape, new questions [J].

Eggermont, Alexander M. M. .

EUROPEAN JOURNAL OF CANCER, 2016, 69 :39-42

[39] Efficacy and safety of nivolumab plus ipilimumab versus nivolumab alone in patients with advanced melanoma: a systematic review and meta-analysis [J].

Cui, Shuting ;

Sun, Xiaozhe ;

Gao, Junxi .

EXPERT REVIEW OF ANTICANCER THERAPY, 2024, 24 (05) :283-291

[40] A major responder to ipilimumab and nivolumab in metastatic uveal melanoma with concomitant autoimmunity [J].

Chan, Pui Ying ;

Hall, Peter ;

Hay, Gordon ;

Cohen, Victoria M. L. ;

Szlosarek, Peter W. .

PIGMENT CELL & MELANOMA RESEARCH, 2017, 30 (06) :558-562

← 1 2 3 4 5 →