TY - JOUR
T1 - Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061)
T2 - a randomised, open-label, controlled, phase 3 trial
AU - KEYNOTE-061 investigators
AU - Shitara, Kohei
AU - Özgüroğlu, Mustafa
AU - Bang, Yung Jue
AU - Di Bartolomeo, Maria
AU - Mandalà, Mario
AU - Ryu, Min Hee
AU - Fornaro, Lorenzo
AU - Olesiński, Tomasz
AU - Caglevic, Christian
AU - Chung, Hyun C.
AU - Muro, Kei
AU - Goekkurt, Eray
AU - Mansoor, Wasat
AU - McDermott, Raymond S.
AU - Shacham-Shmueli, Einat
AU - Chen, Xinqun
AU - Mayo, Carlos
AU - Kang, S. Peter
AU - Ohtsu, Atsushi
AU - Fuchs, Charles S.
AU - Lerzo, Guillermo
AU - O'Connor, Juan Manuel
AU - Mendez, Guillermo Ariel
AU - Lynam, James
AU - Tebbutt, Niall
AU - Wong, Mark
AU - Strickland, Andrew
AU - Karapetis, Chris
AU - Goldstein, David
AU - Vasey, Paul
AU - Van Laethem, Jean Luc
AU - Van Cutsem, Eric
AU - Berry, Scott
AU - Vincent, Mark
AU - Muller, Bettina
AU - Rey, Felipe
AU - Zambrano, Angela
AU - Guerra, Joaquin
AU - Krogh, Merete
AU - Baeksgaard, Lene
AU - Yilmaz, Mette
AU - Elme, Anneli
AU - Magi, Andrus
AU - Auvinen, Paivi
AU - Alanko, Tuomo
AU - Moehler, Markus
AU - Kunzmann, Volker
AU - Seufferlein, Thomas
AU - Thuss-Patience, Peter
AU - Goekkurt, Eray
AU - Hoehler, Thomas
AU - Haag, Georg
AU - Al-Batran, Salah Eddin
AU - Castro, Hugo
AU - Lopez, Karla
AU - Aguilar Vasquez, Mynor
AU - Sandoval, Mario
AU - Lam, Ka On
AU - Cuffe, Sinead
AU - Kelly, Cathy
AU - Geva, Ravit
AU - Shacham-Shmueli, Einat
AU - Hubert, Ayala
AU - Beny, Alex
AU - Brenner, Baruch
AU - Giuseppe, Aprile
AU - Falcone, Alfredo
AU - Maiello, Evaristo
AU - Passalacqua, Rodolfo
AU - Montesarchio, Vincenzo
AU - Hara, Hiroki
AU - Chin, Keisho
AU - Nishina, Tomohiro
AU - Komatsu, Yoshito
AU - Machida, Nozumo
AU - Hironaka, Shuichi
AU - Satoh, Taroh
AU - Tamura, Takao
AU - Sugimoto, Naotaoshi
AU - Cho, Haruhiko
AU - Omuro, Yashushi
AU - Kato, Ken
AU - Goto, Masahiro
AU - Hyodo, Ichinosuke
AU - Yoshida, Kazuhiro
AU - Baba, Hideo
AU - Esaki, Taito
AU - Furuse, Junji
AU - Wan Mohammed, Wan Zamaniah
AU - Hernandez Hernandez, Carlos
AU - Casas Garcia, Juan
AU - Dominguez Andrade, Adriana
AU - Clarke, Katriona
AU - Hjortland, Geir
AU - Glenjen, Nils
AU - Kubiatowski, Tomasz
AU - Jacek, Jassem
AU - Wojtukiewicz, Marek
AU - Lazarev, Sergey
AU - Lancukhay, Yuri
AU - Afanasayev, Sergey
AU - Moiseyenko, Vladimir
AU - Kostorov, Vladimir
AU - Protsenko, Svetlana
AU - Shirinkin, Vadim
AU - Sakaeva, Dina
AU - Fadeeva, Natalia
AU - Yong, Wei Peng
AU - Ng, Chau Hsien Matthew
AU - Robertson, Barbara
AU - Rapaport, Bernardo
AU - Cohen, Graham
AU - Dreosti, Lydia
AU - Ruff, Paul
AU - Jacobs, Conrad
AU - Landers, Gregory
AU - Szpak, Waldemar
AU - Roh, Sang Young
AU - Lee, Jeeyun
AU - Kim, Yeul Hong
AU - Bang, Yung Jue
AU - Chung, Hyun Cheol
AU - Ryu, Min Hee
AU - Alsina Maqueda, Maria
AU - Longo Munoz, Federico
AU - Cervantes Aguilar, Andres
AU - Aranda Aguilar, Enrique
AU - Garcia Alfonso, Pilar
AU - Rivera, Fernando
AU - Feliu Batle, Jaime
AU - Pazo Cid, Roberto
AU - Yeh, Kun Huei
AU - Chen, Jen Shi
AU - Chao, Yee
AU - Yen, Chia Jui
AU - Özgüroğlu, Mustafa
AU - Kara, Oguz
AU - Yalcin, Suayib
AU - Hochhauser, Daniel
AU - Chau, Ian
AU - Benson, Al
AU - Shankaran, Veena
AU - Shaib, Walid
AU - Philip, Philip
AU - Sharma, Vivek
AU - Siegel, Robert
AU - Sun, Weijing
AU - Wainberg, Zev
AU - George, Ben
AU - Bullock, Andrea
AU - Myrick, Samuel
AU - Faruol, Josephine
AU - Siegel, Richard
AU - Larson, Timothy
AU - Becerra, Carlos
AU - Ratnam, Suresh
AU - Richards, Donald A.
AU - Riche, Stephen L.
PY - 2018/7/14
Y1 - 2018/7/14
N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co.
AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co.
UR - http://www.scopus.com/inward/record.url?scp=85048592368&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(18)31257-1
DO - 10.1016/S0140-6736(18)31257-1
M3 - Article
C2 - 29880231
AN - SCOPUS:85048592368
VL - 392
SP - 123
EP - 133
JO - Lancet
JF - Lancet
SN - 0140-6736
IS - 10142
ER -