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

97 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 (US)
Pages (from-to)123-133
Number of pages11
JournalThe Lancet
Volume392
Issue number10142
DOIs
StatePublished - Jul 14 2018

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{b325a81e782945de950420a0be430643,
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.",
author = "{KEYNOTE-061 investigators} and Kohei Shitara and Mustafa {\"O}zg{\"u}roğlu and Bang, {Yung Jue} and {Di Bartolomeo}, Maria and Mario Mandal{\`a} and Ryu, {Min Hee} 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 Guillermo Lerzo and O'Connor, {Juan Manuel} and Mendez, {Guillermo Ariel} and James Lynam and Niall Tebbutt and Mark Wong and Andrew Strickland and Chris Karapetis and David Goldstein and Paul Vasey and {Van Laethem}, {Jean Luc} and {Van Cutsem}, Eric and Scott Berry and Mark Vincent and Bettina Muller and Felipe Rey and Angela Zambrano and Joaquin Guerra and Merete Krogh and Lene Baeksgaard and Mette Yilmaz and Anneli Elme and Andrus Magi and Paivi Auvinen and Tuomo Alanko and Markus Moehler and Volker Kunzmann and Thomas Seufferlein and Peter Thuss-Patience and {Benson III}, {Al B}",
year = "2018",
month = "7",
day = "14",
doi = "10.1016/S0140-6736(18)31257-1",
language = "English (US)",
volume = "392",
pages = "123--133",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10142",

}

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.

In: The Lancet, Vol. 392, No. 10142, 14.07.2018, p. 123-133.

Research output: Contribution to journalArticle

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 - Benson III, Al B

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.

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

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

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SP - 123

EP - 133

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10142

ER -