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
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (168)
Lucjan Wyrwicz
Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Nina Karaseva
SPb SBHI Clinical Oncology Dispensary, St Petersburg, Russia
Mikhail Osipov
Leningrad Regional Clinical Hospital, St Petersburg, Russian Federation
Sergey Afanasyev
Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation
Salah Eddin Al-Batran
The Frankfurt Institute of Clinical Cancer Research, Frankfurt, Germany
Patricio Yáñez
Filippo Pietrantonio
Xiao Fang
Yanfen Guan
Merck & Co, Inc, Rahway, NJ
Adriana Valderrama
Merck & Co, Inc, Rahway, NJ
Pierre Leconte
MSD France, Puteaux, France
Pooja Bhagia
Merck & Co, Inc, Rahway, NJ
Yung-Jue Bang
Seoul National University College of Medicine; Seoul National University Graduate School, Seoul, South Korea
Marc Van Den Eynde
Cliniques Universitaires St-Luc, Brussels, Belgium
Amelie Deleporte
Phillippe Vergauwe
Joelle Collignon
Eric Van Cutsem
University Hospitals Gasthuisberg, Leuven, Belgium
Lionel D. Hondt
Arinilda Campos Bragagnoli
Barretos Cancer Center, Barretos, Brazil
Rafael Balsini Barreto
Kathia Cristina Abdalla
Centro Integrado de Pesquisa (CIP), Hospital de Base de São José do Rio Preto, São José Do Rio Preto, Brazil
Maria Ignez Freitas Melro Braghiroli
Jamille Gonzaga Dutra
Diogo Bugano Diniz Gomes
Department of Oncology, Hospital Israelita Albert Einstein, São Paulo, Brazil; Hospital Municipal Vila Santa Catarina, São Paulo, Brazil
Maria Marcela Fernandes Monteiro
Petr Kavan
Frederic Lemay
Mahmoud Abdelsalam
Mai-Kim Gervais
Sebastian Mondaca
Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile
Luis Villanueva
Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago, Chile
Patricio Eduardo Yanez Weber
Oncology-Hematology Unit, Department of Internal Medicine, School of Medicine, Universidad de la Frontera, Temuco, Chile
Plinio Fernandez
Jiafu Ji
Jiongqiang Huang
Jing Zhuang
Luchuan Chen
Xiangdong Cheng
Quan Wang
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases
Yongjian Zhou
Qun Zhao
State Key Laboratory of Medical Proteomics, National Chromatographic Research & Analysis Center, Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Zhongtao Zhang
Congqiao Jiang
Leping Li
State Key Laboratory of Crystal Materials Tianjin Key Laboratory of Functional Crystal Materials School of Integrated Circuit Science and Engineering Tianjin University of Technology Tianjin China
Hui Cao
Chao Gao
Xianli He
Ping Zhao
Yiping Mou
Anneli Elme
Guillaume Piessen
Pascal Artru
Christophe Louvet
Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France
Olivier Bouche
Samuel Le Sourd
Department of Medical Oncology, Centre Eugène-Marquis, Rennes, France
David Tougeron
Department of Hepatology and Gastroenterology, Poitiers University Hospital, Poitiers, France
Hélène Senellart
Department of Medical Oncology, Comprehensive Cancer Center, Institut de Cancérologie de l'Ouest, Saint-Herblain, France
Rosine Guimbaud
Thierry André
Emmanuel Mitry
Medical Oncology Department, Institute Paoli-Calmettes, Marseille, France
Antoine Adenis
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM, University of Montpellier, Montpellier Cancer Institute (ICM), Montpellier, France
Jean-Philippe Metges
Institut de Cancérologie et d’Imagerie, Arpego Network, Centre Hospitalier Universitaire de Brest, Brest, France
Michael Stahl
Volker Heinemann
Gunnar Folprecht
From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...
Arndt Vogel
Markus K. Diener
Guido Hausner
Eray Goekkurt
Markus H. Moehler
Department of Internal Medicine I, Johannes Gutenberg-University Clinic, Mainz, Germany
Marco Antonio Chivalan
Hugo Raul Castro
Pier Anyelo Ramos Elias
Irit Ben-Aharon
Division of Oncology, Rambam Health Care Center, Haifa, Israel
Sharon Pelles Avraham
Ayala Hubert
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Baruch Brenner
Sofia Man
Moshe Mishaeli
Einat Shacham-Shmueli
Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel
Andrea Spallanzani
University Hospital of Modena, Modena, Italy
Maria Di Bartolomeo
Sara Lonardi
Armando Santoro
IRCCS Humanitas Research Hospital, Milan
Alberto GianLuigi Luporini
Giovanni Gerardo Cardellino
Department of Oncology, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
Kazumasa Fujitani
Yoshito Komatsu
Naotoshi Sugimoto
Osaka International Cancer Institute, Osaka, Japan
Yukinori Kurokawa
Masahide Kaji
Department of Surgery, Toyama Prefectural Central Hospital, Toyama, Japan
Masaaki Iwatsuki
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University
Seiji Ito
Akitaka Makiyama
Takashi Oshima
Kanagawa Cancer Center, Yokohama, Japan
Masahiro Goto
Hiroshi Yabusaki
Niigata Cancer Center Hospital, Niigata, Japan
Hiroki Hara
Saitama Cancer Center, Ina, Japan
Yasuhiro Choda
Hiroshima City Hospital, Hiroshima, Japan
Masaru Morita
Department of Gastroenterological Surgery, NHO Kyushu Cancer Center, Fukuoka, Japan
Eiji Oki
Hirofumi Yasui
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
Kenji Amagai
Kohei Shitara
Takaki Yoshikawa
National Cancer Center Hospital, Tokyo, Japan
Yoshihiro Nabeya
Hisateru Yasui
Masahiro Tsuda
Tatsu Shimoyama
1Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
Keisuke Koeda
Kensei Yamaguchi
Tomohiro Nishina
Department of Gastrointestinal Medical Oncology, NHO Shikoku Cancer Center, Matsuyama, Japan
Yu Sunakawa
Kazuhide Ozaki
Nobuhiro Shibata
Zanete Zvirbule
Anastasija Ranceva
Edita Baltruskeviciene
National Cancer Institute, Verkiai, VA, Lithuania
Gwo Fuang Ho
University Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia
Rubi K. Li
Lucjan Stanislaw Wyrwicz
Wojciech Polkowski
Piotr Jan Wysocki
Department of Oncology, Jagiellonian University Medical College Hospital, Kraków, Poland
Magdalena Sobala
Dorota Garncarek-Lange
Wieslaw Bal
Michael Osipov
Nina A. Karaseva
St Petersburg State Budgetary Institution of Healthcare Clinical Oncology Dispensary, St Petersburg, Russian Federation
Sergey G. Afanasyev
Vladimir Ya. Melnichenko
Alexey Mikhailovich Karachun
Igor Yurievich Kudryavtsev
Alexey Alexandrovich Tryakin
Maria Smagina
Wei Peng Yong
Chau Hsien Matthew Ng
Do-Youn Oh
Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, and the Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
Sun Young Rha
Min-Hee Ryu
Asan Medical Center, Seoul, South Korea
Young-Kyu Park
Chonnam National University Medical School, Hwasun, Republic of Korea
Jwahoon Kim
Keun-Wook Lee
Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
In Sil Choi
Sun Jin Sym
Hei-Cheul Jeung
Kun-Huei Yeh
National Taiwan University Hospital; National Taiwan University College of Medicine, Taipei, Taiwan
Chun-Nan Yeh
Chang Gung Memorial Hospital at Linkou
Po-Sheng Yang
Hsin-Hsuan Chen
Chia-Jui Yen
Wasat Mansoor
Christie NHS Foundation Trust, Manchester, United Kingdom
Ian Chau
Won Ho Edward Park
Daniel Krell
Russell Petty
Stephen Falk
Bristol Cancer Institute, Bristol, United Kingdom
Yuriy Ostapenko
Anna Kryzhanivska
Igor Bondarenko
Dniprovsky State Medical University, Dnipro, Ukraine
Hryhoriy Adamchuk
Nataliia Voitko
Ievgen Ilin
Vincent Chung
Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA
Aiwu Ruth He
Columbia University Irving Medical Center, New York, NY
Stacey Stein
Yale Cancer Center, New Haven, CT
Al Benson
Nina Beri