Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial Academic Article uri icon

abstract

  • Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine.This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries. Eligible patients were randomised (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel. Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher. Safety was assessed in all patients, irrespective of CPS. The significance threshold for overall survival was p=0·0135 (one-sided). This trial is registered at ClinicalTrials.gov, number NCT02370498.Between June 4, 2015, and July 26, 2016, 592 patients were enrolled. Of the 395 patients who had a PD-L1 CPS of 1 or higher, 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel. As of Oct 26, 2017, 326 patients in the population with CPS of 1 or higher had died (151 [77%] of 196 patients in the pembrolizumab group and 175 [88%] of 199 patients in the paclitaxel group). Median overall survival was 9·1 months (95% CI 6·2-10·7) with pembrolizumab and 8·3 months (7·6-9·0) with paclitaxel (hazard ratio [HR] 0·82, 95% CI 0·66-1·03; one-sided p=0·0421). Median progression-free survival was 1·5 months (95% CI 1·4-2·0) with pembrolizumab and 4·1 months (3·1-4·2) with paclitaxel (HR 1·27, 95% CI 1·03-1·57). In the total population, grade 3-5 treatment-related adverse events occurred in 42 (14%) of the 294 patients treated with pembrolizumab and 96 (35%) of the 276 patients treated with paclitaxel.Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher. Pembrolizumab had a better safety profile than paclitaxel. Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing.Merck Sharp & Dohme, a subsidiary of Merck & Co.

authors

  • Shitara, Kohei
  • Özgüroğlu, Mustafa
  • Bang, Yung-Jue
  • Di Bartolomeo, Maria
  • Mandalà, Mario
  • Ryu, Min-Hee
  • Fornaro, Lorenzo
  • Olesiński, Tomasz
  • Caglevic, Christian
  • Chung, Hyun C
  • Muro, Kei
  • Goekkurt, Eray
  • Mansoor, Wasat
  • McDermott, Raymond S
  • Shacham-Shmueli, Einat
  • Chen, Xinqun
  • Mayo, Carlos
  • Kang, S Peter
  • Ohtsu, Atsushi
  • Fuchs, Charles S
  • Lerzo, Guillermo
  • O'Connor, Juan Manuel
  • Mendez, Guillermo Ariel
  • Lynam, James
  • Tebbutt, Niall
  • Wong, Mark
  • Strickland, Andrew
  • Karapetis, Chris
  • Goldstein, David
  • Vasey, Paul
  • Van Laethem, Jean-Luc
  • Van Cutsem, Eric
  • Berry, Scott
  • Vincent, Mark
  • Muller, Bettina
  • Rey, Felipe
  • Zambrano, Angela
  • Guerra, Joaquin
  • Krogh, Merete
  • Baeksgaard, Lene
  • Yilmaz, Mette
  • Elme, Anneli
  • Magi, Andrus
  • Auvinen, Paivi
  • Alanko, Tuomo
  • Moehler, Markus
  • Kunzmann, Volker
  • Seufferlein, Thomas
  • Thuss-Patience, Peter
  • Goekkurt, Eray
  • Hoehler, Thomas
  • Haag, Georg
  • Al-Batran, Salah-Eddin
  • Castro, Hugo
  • Lopez, Karla
  • Aguilar Vasquez, Mynor
  • Sandoval, Mario
  • Lam, Ka On
  • Cuffe, Sinead
  • Kelly, Cathy
  • Geva, Ravit
  • Shacham-Shmueli, Einat
  • Hubert, Ayala
  • Beny, Alex
  • Brenner, Baruch
  • Giuseppe, Aprile
  • Falcone, Alfredo
  • Maiello, Evaristo
  • Passalacqua, Rodolfo
  • Montesarchio, Vincenzo
  • Hara, Hiroki
  • Chin, Keisho
  • Nishina, Tomohiro
  • Komatsu, Yoshito
  • Machida, Nozumo
  • Hironaka, Shuichi
  • Satoh, Taroh
  • Tamura, Takao
  • Sugimoto, Naotaoshi
  • Cho, Haruhiko
  • Omuro, Yashushi
  • Kato, Ken
  • Goto, Masahiro
  • Hyodo, Ichinosuke
  • Yoshida, Kazuhiro
  • Baba, Hideo
  • Esaki, Taito
  • Furuse, Junji
  • Wan Mohammed, Wan Zamaniah
  • Hernandez Hernandez, Carlos
  • Casas Garcia, Juan
  • Dominguez Andrade, Adriana
  • Clarke, Katriona
  • Hjortland, Geir
  • Glenjen, Nils
  • Kubiatowski, Tomasz
  • Jacek, Jassem
  • Wojtukiewicz, Marek
  • Lazarev, Sergey
  • Lancukhay, Yuri
  • Afanasayev, Sergey
  • Moiseyenko, Vladimir
  • Kostorov, Vladimir
  • Protsenko, Svetlana
  • Shirinkin, Vadim
  • Sakaeva, Dina
  • Fadeeva, Natalia
  • Yong, Wei Peng
  • Ng, Chau Hsien Matthew
  • Robertson, Barbara
  • Rapaport, Bernardo
  • Cohen, Graham
  • Dreosti, Lydia
  • Ruff, Paul
  • Jacobs, Conrad
  • Landers, Gregory
  • Szpak, Waldemar
  • Roh, Sang-Young
  • Lee, Jeeyun
  • Kim, Yeul Hong
  • Bang, Yung-Jue
  • Chung, Hyun Cheol
  • Ryu, Min-Hee
  • Alsina Maqueda, Maria
  • Longo Munoz, Federico
  • Cervantes Aguilar, Andres
  • Aranda Aguilar, Enrique
  • Garcia Alfonso, Pilar
  • Rivera, Fernando
  • Feliu Batle, Jaime
  • Pazo Cid, Roberto
  • Yeh, Kun-Huei
  • Chen, Jen-Shi
  • Chao, Yee
  • Yen, Chia-Jui
  • Özgüroğlu, Mustafa
  • Kara, Oguz
  • Yalcin, Suayib
  • Hochhauser, Daniel
  • Chau, Ian
  • Benson, Al
  • Shankaran, Veena
  • Shaib, Walid
  • Philip, Philip
  • Sharma, Vivek
  • Siegel, Robert
  • Sun, Weijing
  • Wainberg, Zev
  • George, Ben
  • Bullock, Andrea
  • Myrick, Samuel
  • Faruol, Josephine
  • Siegel, Richard
  • Larson, Timothy
  • Becerra, Carlos
  • Ratnam, Suresh
  • Richards, Donald A
  • Riche, Stephen L

publication date

  • July 2018

published in