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
Kohei Shitara, Sun Young Rha, Lucjan Wyrwicz, Takashi Oshima, Nina Karaseva, Mikhail Osipov, Hisateru Yasui, Hiroshi Yabusaki, S. G. Afanasyev, Young Kyu Park, S. Al-Batran, Takaki Yoshikawa, Patricio Yañez, Filippo Pietrantonio, Sara Lonardi, Xiao Fang, Yanfen Guan, Adriana Valderrama, Pierre Leconte, Pooja Bhagia, Yung‐Jue Bang, on behalf of the KEYNOTE-585 Investigators, Marc Van den Eynde, Amélie Deleporte, Phillippe Vergauwe, Joëlle Collignon, Eric Van Cutsem, Lionel D. Hondt, Arinilda Campos Bragagnoli, Rafael Balsini Barreto, Kathia Cristina Abdalla, Maria Ignez Braghiroli, Jamille Dutra, Diogo Bugano Diniz Gomes, Maria Marcela Fernandes Monteiro, Petr Kavan, Frédéric Lemay, Mahmoud Abdelsalam, Mai‐Kim Gervais, Sebastián Mondaca, Luis J. Villanueva-Rivera, P.E. Yanez Weber, Plinio Fernández, Jiafu Ji, Jiongqiang Huang, Jing Zhuang, Luchuan Chen, Xiangdong Cheng, Quan Wang, Yongjian Zhou, Qun Zhao, Zhong-Tao Zhang, Congqiao Jiang, Leping Li, Hui Cao, Chao Gao, Xianli He, Ping Zhao, Yiping Mou, Anneli Elme, Guillaume Piessen, Pascal Artru, Christophe Louvet, Olivier Bouché, Samuel Le Sourd, David Tougeron, Hélène Senellart, Rosine Guimbaud, Thierry André, Emmanuel Mitry, Antoine Adenis, Jean‐Philippe Metges, M. Stahl, Volker Heinemann, Gunnar Folprecht, Arndt Vogel, Markus K. Diener, Guido Hausner, Eray Goekkurt, Markus Moehler, Marco Chivalan, Hugo R. Castro, Pier Anyelo Ramos Elias, Irit Ben‐Aharon, Sharon Pelles Avraham, Ayala Hubert, Baruch Brenner, Sofia Man, Moshe Mishaeli, Einat Shacham‐Shmueli, Andrea Spallanzani, Maria Di Bartolomeo, Sara Lonardi, Armando Santoro, Alberto Luporini, Giovanni Gerardo Cardellino, Kazumasa Fujitani, Yoshito Komatsu, Naotoshi Sugimoto, Yukinori Kurokawa
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.