Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial

被引：27

作者：

Eggermont, Alexander M. M. ^{[1
,2
,3
,4
]}

Kicinski, Michal ^{[5
]}

Blank, Christian U. ^{[6
]}

Mandala, Mario ^{[7
]}

V. Long, Georgina ^{[8
,9
]}

Atkinson, Victoria ^{[10
]}

Dalle, Stephane ^{[11
]}

Haydon, Andrew ^{[12
]}

Meshcheryakov, Andrey ^{[13
]}

Khattak, Adnan ^{[11
,14
,15
]}

Carlino, Matteo S. ^{[16
]}

Sandhu, Shahneen ^{[17
]}

Larkin, James ^{[18
]}

Puig, Susana ^{[19
,20
]}

Ascierto, Paolo A. ^{[21
]}

Rutkowski, Piotr ^{[22
]}

Schadendorf, Dirk ^{[23
,24
]}

Boers-Sonderen, Marye ^{[25
]}

Di Giacomo, Anna Maria ^{[26
,27
]}

van den Eertwegh, Alfonsus J. M. ^{[28
]}

Grob, Jean-Jacques ^{[29
]}

Gutzmer, Ralf ^{[30
]}

Jamal, Rahima ^{[31
]}

van Akkooi, Alexander C. J. ^{[32
,33
]}

Lorigan, Paul ^{[34
,35
]}

Grebennik, Dmitri ^{[36
]}

Kreplere, Clemens ^{[36
]}

Marreaud, Sandrine ^{[5
]}

Suciu, Stefan ^{[5
]}

Robert, Caroline ^{[37
,38
]}

机构：

[1] Tech Univ Munich, Comprehens Canc Ctr Munich, Munich, Germany

[2] Ludwig Maximilians Univ Munchen, Munich, Germany

[3] Princess Maxima Ctr, Utrecht, Netherlands

[4] Univ Med Ctr Utrecht, Utrecht, Netherlands

[5] EORTC Headquarters, Brussels, Belgium

[6] Netherlands Canc Inst Antoni Van Leeuwenhoek, Amsterdam, Netherlands

[7] Univ Perugia, Santa Maria Misericordia Hosp, Perugia, Italy

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

[9] Mater & Royal North Shore Hosp, Sydney, Australia

[10] Univ Queensland, Princess Alexandra Hosp, Brisbane, Australia

[11] Lyon Univ, HCL Canc Inst, Canc Res Ctr Lyon, Lyon, France

[12] Alfred Hosp, Melbourne, Australia

[13] Fed Med Biol Agcy, Lopukhin Fed Res & Clin Ctr Phys Chem Med, Moscow, Russia

[14] Univ Western Australia, Fiona Stanley Hosp, Perth, Australia

[15] Edith Cowan Univ, Perth, Australia

[16] Melanoma Inst Australia, Westmead & Blacktown Hosp, Sydney, NSW, Australia

[17] Peter MacCallum Canc Ctr, Melbourne, Australia

[18] Royal Marsden Hosp, London, England

[19] Univ Barcelona, Hosp Clin Barcelona, Barcelona, Spain

[20] CIBERER, Inst Salud Carlos III, Barcelona, Spain

[21] Ist Nazl Tumori IRCCS Fdn G Pascale, Naples, Italy

[22] Mar Sklodowska Curie Natl Res Inst Oncol, Warsaw, Poland

[23] Univ Hosp Essen, Essen, Germany

[24] German Canc Consortium, Heidelberg, Germany

[25] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands

[26] Univ Siena, Siena, Italy

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

[28] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands

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

[30] Ruhr Univ Bochum, Johannes Wesling Med Ctr, Campus Minden, Minden, Germany

[31] Ctr Hosp Univ Montreal CHUM, Ctr Rech CHUM, Montreal, PQ, Canada

[32] Univ Sydney, Melanoma Inst Australia, Fac Med & Hlth, Wollstonecraft Sydney, Camperdown, NSW, Australia

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

[34] Univ Manchester, Div Canc Sci, Manchester, England

[35] Christie NHS Fdn Trust, Manchester, England

[36] Merck & Co Inc, Rahway, NJ USA

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

[38] Univ Paris Saclay, Villejuif, France

来源：

EUROPEAN JOURNAL OF CANCER | 2024年 / 211卷

关键词：

Anti-PD1; Anti-PDL1; Clinical trial; Immune checkpoint inhibitors; Melanoma; Phase; 3; Immunotherapy; Pembrolizumab; Adjuvant treatment; METASTASIS-FREE SURVIVAL; DOUBLE-BLIND; COMPLETE RESECTION; IPILIMUMAB; NIVOLUMAB;

D O I：

10.1016/j.ejca.2024.114327

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) than placebo in patients with resected high risk stage III melanoma. Stability of these benefits when the median follow-up was 3.5 and 5 years was published. Here we report results with a longer follow-up. Methods: We randomized 1019 patients to receive pembrolizumab 200 mg or placebo, intravenously every 3 weeks for a total of 18 doses. RFS in the overall population and in the subgroup of patients with melanoma positive for the PD-1 ligand (PD-L1) were co-primary endpoints. DMFS in these two populations was a secondary and progression/recurrence-free survival 2 (PRFS2) an exploratory endpoint. Results: The median follow-up was 6.9 years. In the overall intention-to-treat population, RFS was longer in the pembrolizumab group than in the placebo group (HR 0.63, 95 % CI 0.53 to 0.74). RFS at 7 years was 50 % (95 % CI 46 % to 55 %) in the pembrolizumab and 36 % (95 % CI 32 % to 41 %) in the placebo group. Positive effects were present both for loco-regional recurrences and distant metastases, and across substages IIIA-IIIB-IIIC, and PD-L1 positive and PD-L1 negative as well as for BRAF mutant and BRAF wild type populations. DMFS was longer in the pembrolizumab group than in the placebo group (HR 0.64, 95 % CI 0.54 to 0.76). DMFS at 7 years was 54 % (95 % CI 50 % to 59 %) in the pembrolizumab and 42 % (95 % CI 37 % to 46 %) in the placebo group. PRFS2 was longer in the pembrolizumab group than in the placebo group (HR 0.69, 95 % CI 0.57 to 0.84). PRFS2 at 7 years was 61 % (95 % CI 57 % to 66 %) in the pembrolizumab and 53 % (95 % CI 49 % to 57 %) in the placebo group. Conclusions: The 7-year analysis of adjuvant therapy with pembrolizumab demonstrated a sustained improvement in the long-term RFS, DMFS and PRFS2 compared with placebo in patients with resected stage III melanoma.

引用

页数：10

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