Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase III trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma

被引：20

作者：

Eggermont, Alexander M. M. ^{[1
,2
]}

Meshcheryakov, Andrey ^{[3
]}

Atkinson, Victoria ^{[4
]}

Blank, Christian U. ^{[5
]}

Mandala, Mario ^{[6
,34
]}

Long, Georgina, V ^{[7
,35
]}

Barrow, Catherine ^{[8
]}

Di Giacomo, Anna Maria ^{[9
]}

Fisher, Rosalie ^{[10
,36
]}

Sandhu, Shahneen ^{[11
]}

Kudchadkar, Ragini ^{[12
]}

Romero, Pablo Luis Ortiz ^{[13
]}

Svane, Inge Marie ^{[14
]}

Larkin, James ^{[15
]}

Puig, Susana ^{[16
]}

Hersey, Peter ^{[17
]}

Quaglino, Pietro ^{[18
]}

Queirolo, Paola ^{[19
,37
]}

Stroyakovskiy, Daniil ^{[20
]}

Bastholt, Lars ^{[21
]}

Mohr, Peter ^{[22
]}

Hernberg, Micaela ^{[23
]}

Chiarion-Sileni, Vanna ^{[24
]}

Strother, Matthew ^{[25
]}

Hauschild, Axel ^{[26
]}

Yamazaki, Naoya ^{[27
]}

van Akkooi, Alexander Cj ^{[5
]}

Lorigan, Paul ^{[28
,29
]}

Krepler, Clemens ^{[30
]}

Ibrahim, Nageatte ^{[30
]}

Marreaud, Sandrine ^{[31
]}

Kicinski, Michal ^{[31
]}

Suciu, Stefan ^{[31
]}

Robert, Caroline ^{[32
,33
]}

机构：

[1] Princess Maxima Ctr, NL-3584 CS Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, NL-3584 CS Utrecht, Netherlands

[3] Fed State Budgetary Inst Russian Oncol Sci Ctr, Moscow, Russia

[4] Univ Queensland, Princess Alexandra Hosp, Brisbane, Qld, Australia

[5] Netherlands Canc Inst Antoni van Leeuwenhoek, Amsterdam, Netherlands

[6] Azienda Osped Papa Giovanni XXIII, Bergamo, Italy

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

[8] Wellington Hosp, Wellington, New Zealand

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

[10] North Shore Hosp, Waitemata DHB, Auckland, New Zealand

[11] Peter Maccallum Canc Ctr, Melbourne, Vic, Australia

[12] Emory Univ, Atlanta, GA 30322 USA

[13] Univ Complutense, Med Sch, CIBERONC, Hosp 12 Octubre,Inst i 12, Madrid, Spain

[14] Univ Copenhagen, Herlev Hosp, Herlev, Denmark

[15] Royal Marsden Hosp Chelsea, London, England

[16] Hosp Clin Univ Barcelona, Barcelona, Spain

[17] David Maddison Clin Sci, Gateshead, Australia

[18] Osped San Lazzaro, Azienda Osped Citta Salute & Sci Torino, Turin, Italy

[19] Ist Nazl Ric Sul Canc, Milan, Italy

[20] Municipal Oncol Hosp 62, Krasnogorskiy, Russia

[21] Odense Univ Hosp, Odense, Denmark

[22] Elbe Kliniken, Buxtehude, Germany

[23] Helsinki Univ Cent Hosp, Helsinki, Finland

[24] Azienda Osped Padova, Padua, Italy

[25] Christchurch Hosp, Christchurch, New Zealand

[26] Univ Klinikum Schleswig Holstein, Klin Dermatol Venerol & Allergol, Campus Kiel, Kiel, Germany

[27] Natl Canc Ctr, Chuo Ku, Tokyo, Japan

[28] Univ Manchester, Manchester, Lancs, England

[29] Christie NHS Fdn Trust, Manchester, Lancs, England

[30] Merck & Co Inc, Kenilworth, NJ USA

[31] EORTC Headquarters, Brussels, Belgium

[32] Gustave Roussy Canc Campus Grand Paris, Villejuif, France

[33] Univ Paris Saclay, Villejuif, France

[34] Osped Santa Maria Misericordia, Perrugia, Italy

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

[36] Auckland City Hosp, Auckland, New Zealand

[37] European Inst Oncol IRCCS, Milan, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 158卷

关键词：

Melanoma; anti-PD-1; Pembrolizumab; Salvage treatment; NODE-POSITIVE MELANOMA; DOUBLE-BLIND; ADJUVANT IPILIMUMAB; MULTICENTER; NIVOLUMAB; SURVIVAL;

D O I：

10.1016/j.ejca.2021.09.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: In the phase III double-blind European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 trial, pembrolizumab improved recurrence free and distant metastasis-free survival in patients with stage III cutaneous melanoma with complete resection of lymph nodes. In the pembrolizumab group, the incidence of grade I-V and of grade III-V immune-related adverse events (irAEs) was 37% and 7%, respectively. Methods: Patients were randomised to receive intravenous (i.v.) pembrolizumab 200 mg (N = 514) or placebo (N = 505) every 3 weeks, up to 1 year. On recurrence, patients could enter part 2 of the study: pembrolizumab 200 mg i.v. every 3 weeks up to 2 years, for crossover (those who received placebo) or rechallenge (those who had recurrence >6 months after completing 1-year adjuvant pembrolizumab therapy). For these patients, we present the safety profile and efficacy outcomes. Results: At the clinical cut-off (16-Oct-2020), in the placebo group, 298 patients had a disease recurrence, in which 155 (52%) crossed over ('crossover'). In the pembrolizumab group, 297 patients completed the 1-year treatment period; 47 had a recurrence >6 months later, in which 20 (43%) entered the rechallenge part 2 ('rechallenge'). In the crossover group, the median progression-free survival (PFS) was 8.5 months (95% confidence interval [CI] 5.7-15.2) and the 3-year PFS rate was 32% (95% CI 25-40%). Among 80 patients with stage IV evaluable disease, 31 (39%) had an objective response: 14 (18%) patients with complete response (CR) and 17 (21%) patients with partial response. The 2-year PFS rate from response was 69% (95% CI 48-83%). In the rechallenge group, the median PFS was 4.1 months (95% CI 2.6-NE). Among 9 patients with stage IV evaluable disease, 1 had an objective response (CR). Among the 175 patients, 51 (29%) had a grade I-IV irAE and 11 (6%) had a grade III-IV irAE. Conclusions: Pembrolizumab treatment after crossover yielded an overall 3-year PFS rate of 32% and a 39% ORR in evaluable patients, but the efficacy (11% ORR) was lower in those rechallenged. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：156 / 168

页数：13

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