Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study

We report results of the final analysis of overall survival (OS) and patient-reported outcomes from the phase III KEYNOTE-585 (ClinicalTrials.gov identifier: NCT03221426) study. Participants with previously untreated, locally advanced, resectable gastric and gastroesophageal junction (G/GEJ) cancer were enrolled into the main (n = 804) and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT; n = 203) cohorts, and randomly assigned 1:1 to neoadjuvant and adjuvant pembrolizumab plus chemotherapy or placebo plus chemotherapy. The primary end points were pathologic complete response (pathCR) by central review, event-free survival (EFS) by investigator, OS, and safety. Patient-reported outcomes was an exploratory end point. After a median follow-up of 59.9 months (range, 39-76), median OS was 71.8 versus 55.7 months (hazard ratio [HR], 0.86 [95% CI, 0.71 to 1.06]) with pembrolizumab plus chemotherapy versus placebo plus chemotherapy in the main cohort. The EFS HR was 0.81 (95% CI, 0.67 to 0.98). Grade ≥3 drug-related adverse event rates were 65% versus 63%. Perioperative pembrolizumab plus chemotherapy did not worsen health-related quality of life versus placebo. Pembrolizumab plus chemotherapy continued to show improved outcomes in pathCR and a trend toward longer EFS versus placebo in the main and main plus FLOT cohorts. Efficacy and safety outcomes with perioperative pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in participants with untreated, locally advanced resectable G/GEJ cancer were consistent with previous analyses.

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Journal
Journal of Clinical Oncology
Published
2025-08-19
DOI
https://doi.org/10.1200/jco-25-00486
Citations
17
Primary Topic
Gastric Cancer Management and Outcomes
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article
Field-Weighted Citation Impact
25.81
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article

Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study

Pooja Bhagia, Anneli Elme, Guido Hausner, Jing Zhuang et al.
17 citations
Journal of Clinical Oncology
Gastric Cancer Management and Outcomes
25.81
article

Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study

Pooja Bhagia, Anneli Elme, Guido Hausner, Jing Zhuang, Wei Peng Yong, Young Kyu Park, Chao Gao, Hiroki Hara, Wieslaw Bal, Petr Kavan, Kathia Cristina Abdalla, Stephen Falk, Sharon Pelles Avraham, Markus Moehler, Eray Goekkurt, Stacey Stein, Irit Ben‐Aharon, Gwo Fuang Ho, Yu Sunakawa, Hsin-Hsuan Chen, Sun Jin Sym, Kenji Amagai, Jamille Dutra, Alberto Luporini, Igor Bondarenko, Gunnar Folprecht, Luis J. Villanueva-Rivera, Edita Baltruškevičienė, Tatsu Shimoyama, Vincent Chung, M Sobala, Akitaka Makiyama, Hiroshi Yabusaki, Joëlle Collignon, Dorota Garncarek-Lange, Sun Young Rha, Zanete Zvirbule, Ian Chau, Nobuhiro Shibata, Andrea Spallanzani, Masahiro Tsuda, Markus K. Diener, Al B. Benson, Nina Karaseva, Arinilda Campos Bragagnoli, Wungki Park, Rafael Balsini Barreto, Daniel Krell, S. G. Afanasyev, Takaki Yoshikawa, David Tougeron, Nina Beri, Keisuke Koeda, Олександр Войтко, Patricio Yañez, Aiwu Ruth He, Frédéric Lemay, Russell Petty, Christophe Louvet, Plinio Fernández, Hélène Senellart, Leping Li, Yung‐Jue Bang, Philippe Vergauwe, Sara Lonardi, A. Tryakin, M. A. Osipov, Qun Zhao, Mai-Kim Gervais, Baruch Brenner, Yoshihiro Nabeya, Yoshito Komatsu, Anna Kryzhanivska, Lucjan Wyrwicz, Do‐Youn Oh, Naotoshi Sugimoto, Masaaki Iwatsuki, In Sil Choi, Eiji Oki, Hryhoriy Adamchuk, Adriana Valderrama, Amélie Deleporte, Anastasija Ranceva, Hisateru Yasui, Congqiao Jiang, Sebastián Mondaca, Kun‐Huei Yeh, P.E. Yanez Weber, Hugo R. Castro, Pascal Artru, Mahmoud Abdel‐Radi, Piotr Jan Wysocki, Wasat Mansoor, Maria Ignez Braghiroli, Maria Di Bartolomeo, Jwahoon Kim, Olivier Bouché, Giovanni Gerardo Cardellino, А. М. Карачун, Einat Shacham‐Shmueli, Maria Smagina, Filippo Pietrantonio, Thierry André, Jiafu Ji, Arndt Vogel, Moshe Mishaeli, Jean‐Philippe Metges, Yukinori Kurokawa, Sofia Man, Masahide Kaji, Keun‐Wook Lee, Rubi K. Li, Tomohiro Nishina, Yasuhiro Choda, Eric Van Cutsem, Chun‐Nan Yeh, Marco Chivalan, Masaru Morita, Kensei Yamaguchi, Xianli He, Rosine Guimbaud, Lionel D. Hondt, Zhong-Tao Zhang, Seiji Ito, Yongjian Zhou, Quan Wang, Hirofumi Yasui, Maria Marcela Fernandes Monteiro, Masahiro Goto, Luchuan Chen, Chau Hsien Matthew Ng, Pierre Leconte, Diogo Bugano Diniz Gomes, Xiangdong Cheng, M. Stahl, Marc Van den Eynde, Guillaume Piessen, Yanfen Guan, Emmanuel Mitry, Xiao Fang, Pier Anyelo Ramos Elias, Yuriy Ostapenko, Kazuhide Ozaki, I. V. Kudryavtsev, Wojciech Polkowski, Armando Santoro, Chia-Jui Yen, Jiongqiang Huang, Min-Hee Ryu, Hei-Cheul Jeung, Ayala Hubert, Kazumasa Fujitani, Samuel Le Sourd, S. Al-Batran, Ping Zhao, V. Ya. Melnichenko, Po-Sheng Yang, Volker Heinemann, Yiping Mou, Ievgen Ilin, Hui Cao, Antoine Adenis
article en
17 citations

Abstract

We report results of the final analysis of overall survival (OS) and patient-reported outcomes from the phase III KEYNOTE-585 (ClinicalTrials.gov identifier: NCT03221426) study. Participants with previously untreated, locally advanced, resectable gastric and gastroesophageal junction (G/GEJ) cancer were enrolled into the main (n = 804) and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT; n = 203) cohorts, and randomly assigned 1:1 to neoadjuvant and adjuvant pembrolizumab plus chemotherapy or placebo plus chemotherapy. The primary end points were pathologic complete response (pathCR) by central review, event-free survival (EFS) by investigator, OS, and safety. Patient-reported outcomes was an exploratory end point. After a median follow-up of 59.9 months (range, 39-76), median OS was 71.8 versus 55.7 months (hazard ratio [HR], 0.86 [95% CI, 0.71 to 1.06]) with pembrolizumab plus chemotherapy versus placebo plus chemotherapy in the main cohort. The EFS HR was 0.81 (95% CI, 0.67 to 0.98). Grade ≥3 drug-related adverse event rates were 65% versus 63%. Perioperative pembrolizumab plus chemotherapy did not worsen health-related quality of life versus placebo. Pembrolizumab plus chemotherapy continued to show improved outcomes in pathCR and a trend toward longer EFS versus placebo in the main and main plus FLOT cohorts. Efficacy and safety outcomes with perioperative pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in participants with untreated, locally advanced resectable G/GEJ cancer were consistent with previous analyses.

Journal of Clinical OncologyVol. 43(29)
Goethe University Frankfurt (DE), Universidad de La Frontera (CL), Merck & Co., Inc., Rahway, NJ, USA (United States) (US), Seoul National University (KR), Yonsei University (KR), University Health System (US), Kanagawa Prefectural Hospital Organization (JP), Niigata Cancer Center Hospital (JP), Leningrad Regional Cancer Center (RU), Istituto Oncologico Veneto (IT), Research Institute of Medical Genetics of Russian Academy of Medical Sciences (RU), City Clinical Oncology Center (RU), Institute of Clinical Cancer Research (DE), University Hospital Frankfurt (DE), Krankenhaus Nordwest (DE), National Cancer Center Hospital East (JP), Chonnam National University Hwasun Hospital (KR), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Yonsei University Health System (KR), Kobe City Medical Center General Hospital (JP), Kanagawa Cancer Center
Openalex Percentile: Top 0%
Gastric Cancer Management and Outcomes
25.81
DOISourceOpenAlex
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