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

Research output: Contribution to journalArticle

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
JournalLancet (London, England)
Volume392
Issue number10142
DOIs
Publication statusPublished - Jul 14 2018

Fingerprint

Esophageal Neoplasms
Paclitaxel
Stomach
Cell Death
Survival
Ligands
pembrolizumab
Disease-Free Survival
Safety
Drug Therapy
Platinum
Population

Keywords

  • Adenocarcinoma/drug therapy
  • Aged
  • Antibodies, Monoclonal, Humanized/adverse effects
  • Esophageal Neoplasms/drug therapy
  • Esophagogastric Junction/pathology
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Paclitaxel/adverse effects
  • Stomach Neoplasms/drug therapy
  • Survival Rate
  • Treatment Outcome

Cite this

@article{7b70500161a1468484c1745b4d9d739d,
title = "Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial",
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.",
keywords = "Adenocarcinoma/drug therapy, Aged, Antibodies, Monoclonal, Humanized/adverse effects, Esophageal Neoplasms/drug therapy, Esophagogastric Junction/pathology, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Neoplasm Staging, Paclitaxel/adverse effects, Stomach Neoplasms/drug therapy, Survival Rate, Treatment Outcome",
author = "Kohei Shitara and Mustafa {\"O}zg{\"u}roğlu and Yung-Jue Bang and {Di Bartolomeo}, Maria and Mario Mandal{\`a} and Min-Hee Ryu and Lorenzo Fornaro and Tomasz Olesiński and Christian Caglevic and Chung, {Hyun C} and Kei Muro and Eray Goekkurt and Wasat Mansoor and McDermott, {Raymond S} and Einat Shacham-Shmueli and Xinqun Chen and Carlos Mayo and Kang, {S Peter} and Atsushi Ohtsu and Fuchs, {Charles S} and {KEYNOTE-061 investigators}",
note = "Copyright {\circledC} 2018 Elsevier Ltd. All rights reserved.",
year = "2018",
month = "7",
day = "14",
doi = "10.1016/S0140-6736(18)31257-1",
language = "English",
volume = "392",
pages = "123--133",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Lancet Publishing Group",
number = "10142",

}

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 - 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 - KEYNOTE-061 investigators

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

KW - Adenocarcinoma/drug therapy

KW - Aged

KW - Antibodies, Monoclonal, Humanized/adverse effects

KW - Esophageal Neoplasms/drug therapy

KW - Esophagogastric Junction/pathology

KW - Female

KW - Humans

KW - Infusions, Intravenous

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Paclitaxel/adverse effects

KW - Stomach Neoplasms/drug therapy

KW - Survival Rate

KW - Treatment Outcome

U2 - 10.1016/S0140-6736(18)31257-1

DO - 10.1016/S0140-6736(18)31257-1

M3 - Article

C2 - 29880231

VL - 392

SP - 123

EP - 133

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10142

ER -