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

KEYNOTE-061 investigators

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302 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)123-133
Number of pages11
JournalThe Lancet
Volume392
Issue number10142
DOIs
Publication statusPublished - 2018 Jul 14

Bibliographical note

Funding Information:
KS reports personal fees outside the submitted work for serving in a consulting or advisory role from Astellas Pharma, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, and Ono Pharmaceutical; personal fees as honoraria outside the submitted work from Novartis, AbbVie, and Yakult; and grants outside the submitted work from Lilly, Ono Pharmaceutical, Dainippon Sumoitomo Pharma, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharma, and MSD. YJB reports grants to the institution for clinical trials outside the submitted work from AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serono, Bayer, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eli Lilly, Boehringer Ingelheim, MacroGenics, Boston Biomedical, FivePrime, CKD, Ono, Otsuka, Taiho, Takeda, BeiGene, Hanmi, Green Cross, Curis, Daiichi Sankyo, and Astellas and other for serving in a consulting or advisory outside the submitted work from AstraZeneca, Novartis, Genentech/Roche, MSD, Pfizer, Bayer, Bristol-Myers Squibb, Eli Lilly, Merck Serono, FivePrime, Taiho, Ono, ADC Therapeutics, Green Cross, and Samyang Biopharm. MM reports personal fees for advisory boards, lectures, and speakers' bureau outside the submitted work from MSD. MHR reports other outside the submitted work for serving in a consultant/advisory role and receiving honorarium from Dae Hwa Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, ONO Pharmaceutical, and Taiho. TO reports personal fees during the conduct of the study for serving as an investigator from Merck & Co. CC reports personal fees outside the submitted work for serving as a speaker from MSD, Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, and Tecnofarma; personal fees outside the submitted work for serving as a principal investigator from MSD, Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Roche, AstraZeneca, Astellas, and Novartis; personal fees outside the submitted work for serving as a consultant or advisory board member from MSD, Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Tecnofarma, AstraZeneca, and Lilly; and personal fees outside the submitted work for participating in a sponsored educational program from MSD, Bristol-Myers Squibb, Boehringer Ingelheim, and Tecnofarma. HCC reports grants outside the submitted work from Lilly, GlaxoSmithKline, MSD, Merck-Serono, Bristol-Myers Squibb/Ono, and Taiho; personal fees outside the submitted word for serving on a speakers' bureau from Merck-Serono, Lilly, and Foundation Medicine; and personal fees outside the submitted work for serving as a consultant from Taiho, Celltrion, MSD, Lilly, Quintiles, Bristol-Myers Squibb, and Merck-Serono. KM reports grants outside the submitted work from Ono Pharmaceutical, MSD, Daiichi Sankyo, Kyowa Hakko Kirin, Shionogi Pharmaceutical, and Gilead Sciences and personal fees outside the submitted work from Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Merck Serono, Eli Lilly, and Takult Honsha. E Goekkurt reports personal fees during the conduct of the study for serving as an investigator from MSD; personal fees outside the submitted work for giving lectures from MSD, Lilly, and Servier; and personal fees outside the submitted work for serving in an advisory role from MSD, Bristol-Myers Squibb, Lilly, Sanofi, Servier, and Merck. RSM reports grants outside the submitted work from Pfizer, Amgen, and Celgene; personal fees outside the submitted work from Clovis, Pfizer, and Bristol-Myers Squibb; and research funding outside the submitted work from Bristol-Myers Squibb, Merck, Bayer, and Janssen. XC reports personal fees during the conduct of the study for serving as a full-time employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA. SPK reports personal fees during the conduct of the study for serving as a full-time employee of Merck Sharp & Dohme, a subsidiary of Merck & Co. CM reports personal fees during the conduct of the study for serving as a full-time employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA. AO reports grants during the conduct of the study from Bristol-Myers Squibb and personal fees during the conduct of the study from Bristol-Myers Squibb, Ono Pharmaceutical Company, and Chugai. CSF reports personal fees outside the submitted work for serving as a consultant from Entrinsic Health, Genentech, Merck & Co, Sanofi, Five Prime Therapeutics, Merrimack, Bayer, Agios, Taiho, Kew, Eli Lilly, and Bain Capital and personal fees outside the submitted work for serving as a board member from CytomX. All other authors declare no competing interests.

Funding Information:
This study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. We thank the patients and their families and caregivers for participating in the study and the following employees of Merck Sharp & Dohme, a subsidiary of Merck & Co: Roger Dansey and Jonathan Cheng for critical review of the manuscript, Linda Sun for statistical support, and Mary Savage for biomarker expertise. Medical writing support in the preparation of this report was provided by Melanie A Leiby (Merck Sharp & Dohme, a subsidiary of Merck & Co).

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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