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Lancet. 2018 Jul 14;392(10142):123-133. doi: 10.1016/S0140-6736(18)31257-1. Epub 2018 Jun 4.

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

Collaborators (138)

Lerzo G, O'Connor JM, Mendez GA, Lynam J, Tebbutt N, Wong M, Strickland A, Karapetis C, Goldstein D, Vasey P, Van Laethem JL, Van Cutsem E, Berry S, Vincent M, Muller B, Rey F, Zambrano A, Guerra J, Krogh M, Baeksgaard L, Yilmaz M, Elme A, Magi A, Auvinen P, Alanko T, Moehler M, Kunzmann V, Seufferlein T, Thuss-Patience P, Goekkurt E, Hoehler T, Haag G, Al-Batran SE, Castro H, Lopez K, Aguilar Vasquez M, Sandoval M, Lam KO, Cuffe S, Kelly C, Geva R, Shacham-Shmueli E, Hubert A, Beny A, Brenner B, Giuseppe A, Falcone A, Maiello E, Passalacqua R, Montesarchio V, Hara H, Chin K, Nishina T, Komatsu Y, Machida N, Hironaka S, Satoh T, Tamura T, Sugimoto N, Cho H, Omuro Y, Kato K, Goto M, Hyodo I, Yoshida K, Baba H, Esaki T, Furuse J, Wan Mohammed WZ, Hernandez Hernandez C, Casas Garcia J, Dominguez Andrade A, Clarke K, Hjortland G, Glenjen N, Kubiatowski T, Jacek J, Wojtukiewicz M, Lazarev S, Lancukhay Y, Afanasayev S, Moiseyenko V, Kostorov V, Protsenko S, Shirinkin V, Sakaeva D, Fadeeva N, Yong WP, Ng CHM, Robertson B, Rapaport B, Cohen G, Dreosti L, Ruff P, Jacobs C, Landers G, Szpak W, Roh SY, Lee J, Kim YH, Bang YJ, Chung HC, Ryu MH, Alsina Maqueda M, Longo Munoz F, Cervantes Aguilar A, Aranda Aguilar E, Garcia Alfonso P, Rivera F, Feliu Batle J, Pazo Cid R, Yeh KH, Chen JS, Chao Y, Yen CJ, Özgüroğlu M, Kara O, Yalcin S, Hochhauser D, Chau I, Benson A, Shankaran V, Shaib W, Philip P, Sharma V, Siegel R, Sun W, Wainberg Z, George B, Bullock A, Myrick S, Faruol J, Siegel R, Larson T, Becerra C, Ratnam S, Richards DA, Riche SL.

Author information

1
National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: kshitara@east.ncc.go.jp.
2
Istanbul University, Cerrahpaşa School of Medicine, Istanbul, Turkey.
3
Seoul National University College of Medicine, Seoul, South Korea.
4
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
5
Papa Giovanni XXIII Hospital, Bergamo, Italy.
6
University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
7
Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
8
Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland.
9
Fundación Arturo López Pérez - Clínica Alemana de Santiago, Santiago, Chile.
10
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
11
Aichi Cancer Center Hospital, Nagoya, Japan.
12
Hematology Oncology Practice Eppendorf (HOPE), Hamburg, Germany; University Cancer Center Hamburg, Hamburg, Germany.
13
Christie Hospital NHS Foundation Trust, Manchester, UK.
14
Adelaide and Meath Hospital, Dublin, Ireland.
15
Sheba Medical Center, Ramat Gan, Israel.
16
Merck & Co, Kenilworth, NJ, USA.
17
National Cancer Center Hospital East, Kashiwa, Japan.
18
Yale Cancer Center, Smilow Cancer Hospital, New Haven, CT, USA.

Abstract

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.

PMID:
29880231
DOI:
10.1016/S0140-6736(18)31257-1
[Indexed for MEDLINE]

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