Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial
2018; Elsevier BV; Volume: 392; Issue: 10142 Linguagem: Inglês
10.1016/s0140-6736(18)31257-1
ISSN1474-547X
AutoresKohei Shitara, Mustafa Özgüroğlu, Yung‐Jue Bang, Maria Di Bartolomeo, Mario Mandalà, Min‐Hee Ryu, Lorenzo Fornaro, Tomasz Olesiński, Christian Caglevic, Hyun Cheol Chung, Kei Muro, Eray Goekkurt, Wasat Mansoor, Ray McDermott, Einat Shacham‐Shmueli, Xinqun Chen, Carlos Mayo, Soonmo Peter Kang, Atsushi Ohtsu, Charles S. Fuchs, Guillermo Lerzo, Juan Manuel O’Connor, Guillermo Ariel Mendez, James Lynam, Niall C. Tebbutt, Mark Wong, Andrew Strickland, Christos S. Karapetis, David Goldstein, Paul L. Vasey, Jean–Luc Van Laethem, Eric Van Cutsem, Scott Berry, Mark Vincent, Bettina Müller, Felipe Rey, Ángela R. Zambrano, Joaquín Guerra, Merete Krogh, Lene Bæksgaard, Mette Yilmaz, Anneli Elme, Andrus Magi, Päivi Auvinen, Tuomo Alanko, Markus Moehler, Volker Kunzmann, Thomas Seufferlein, Peter Thuss-Patience, Eray Goekkurt, Thomas Hoehler, Georg Martin Haag, Salah‐Eddin Al‐Batran, Hugo R. Castro, Karla Alejandra Lopez, Mynor Aguilar Vasquez, Mario Sandoval, Ka On Lam, Sinéad Cuffe, Catherine M. Kelly, Ravit Geva, Einat Shacham‐Shmueli, Ayala Hubert, Alex Beny, Baruch Brenner, Giuseppe Aprile, Alfredo Falcone, Evaristo Maiello, Rodolfo Passalacqua, Vincenzo Montesarchio, Hiroki Hara, Keisho Chìn, Tomohiro Nishina, Yoshito Komatsu, Nozumo Machida, Shuichi Hironaka, Taroh Satoh, Takao Tamura, Naotaoshi Sugimoto, Haruhiko Cho, Yashushi Omuro, Ken Kato, Masahiro Goto, Ichinosuke Hyodo, Kazuhiro Yoshida, Hideo Baba, Taito Esaki, Junji Furuse, Wan Zamaniah Wan Mohammed, Carlos Hernández Hernández, Juan Casas Garcia, Adriana Dominguez Andrade, Katriona Clarke, Geir Olav Hjortland, Nils Glenjen, Tomasz Kubiatowski, Jassem Jacek, Marek Z. Wojtukiewicz, Sergey Lazarev, Yuri Lancukhay, Sergey Afanasayev, Vladimir Moiseyenko, Vladimir Kostorov, Светлана Проценко, Vadim Shirinkin, Dina Sakaeva, Natalia Fadeeva, Wei Peng Yong, Chau Hsien Matthew Ng, Barbara Robertson, Bernardo Rapaport, Graham Cohen, Lydia Dreosti, Paul Ruff, Conrad Jacobs, Gregory Landers, Waldemar Szpak, Sang-Young Roh, Jeeyun Lee, Yeul Hong Kim, Yung‐Jue Bang, Hyun Cheol Chung, Min‐Hee Ryu, María Maqueda, Federico Longo Munoz, A. Aguilar, Enrique Aranda, Pilar Alfonso, Fernando Rivera, Jaime Feliu Batle, Roberto Pazo-Cid, Kun‐Huei Yeh, Jen‐Shi Chen, Yee Chao, Chia‐Jui Yen, Mustafa Özgüroğlu, Oğuz Kara, Şuayib Yalçın, Daniel Hochhauser, Ian Chau, Al B. Benson, Veena Shankaran, Walid L. Shaib, Philip Philip, Vivek Sharma, Robert W. Siegel, Weijing Sun, Zev A. Wainberg, Ben George, Andrea J. Bullock, Samuel Myrick, Josephine Faruol, Richard Siegel, Timothy Larson, Carlos Becerra, Suresh Ratnam, Donald Richards, Stephen L. Riche,
Tópico(s)Gastrointestinal Tumor Research and Treatment
ResumoBackground 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.
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