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Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study

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Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. / Sun, Jong-Mu; Shen, Lin; Shah, Manish A; Enzinger, Peter; Adenis, Antoine; Doi, Toshihiko; Kojima, Takashi; Metges, Jean-Philippe; Li, Zhigang; Kim, Sung-Bae; Cho, Byoung Chul; Mansoor, Wasat; Li, Shau-Hsuan; Sunpaweravong, Patrapim; Maqueda, Maria Alsina; Goekkurt, Eray; Hara, Hiroki; Antunes, Luis; Fountzilas, Christos; Tsuji, Akihito; Oliden, Victor Castro; Liu, Qi; Shah, Sukrut; Bhagia, Pooja; Kato, Ken; KEYNOTE-590 Investigators.

In: LANCET, Vol. 398, No. 10302, 28.08.2021, p. 759-771.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sun, J-M, Shen, L, Shah, MA, Enzinger, P, Adenis, A, Doi, T, Kojima, T, Metges, J-P, Li, Z, Kim, S-B, Cho, BC, Mansoor, W, Li, S-H, Sunpaweravong, P, Maqueda, MA, Goekkurt, E, Hara, H, Antunes, L, Fountzilas, C, Tsuji, A, Oliden, VC, Liu, Q, Shah, S, Bhagia, P, Kato, K & KEYNOTE-590 Investigators 2021, 'Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study', LANCET, vol. 398, no. 10302, pp. 759-771. https://doi.org/10.1016/S0140-6736(21)01234-4

APA

Sun, J-M., Shen, L., Shah, M. A., Enzinger, P., Adenis, A., Doi, T., Kojima, T., Metges, J-P., Li, Z., Kim, S-B., Cho, B. C., Mansoor, W., Li, S-H., Sunpaweravong, P., Maqueda, M. A., Goekkurt, E., Hara, H., Antunes, L., Fountzilas, C., ... KEYNOTE-590 Investigators (2021). Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. LANCET, 398(10302), 759-771. https://doi.org/10.1016/S0140-6736(21)01234-4

Vancouver

Sun J-M, Shen L, Shah MA, Enzinger P, Adenis A, Doi T et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. LANCET. 2021 Aug 28;398(10302):759-771. https://doi.org/10.1016/S0140-6736(21)01234-4

Bibtex

@article{9c6be833c2844d0b950d5a91e0b67d43,
title = "Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study",
abstract = "BACKGROUND: First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer.METHODS: We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment.FINDINGS: Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group.INTERPRETATION: Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population.FUNDING: Merck Sharp & Dohme.",
keywords = "Antibodies, Monoclonal, Humanized/therapeutic use, Antineoplastic Agents, Immunological/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Cisplatin/therapeutic use, Double-Blind Method, Esophageal Neoplasms/drug therapy, Female, Fluorouracil/therapeutic use, Humans, Male, Middle Aged, Squamous Cell Carcinoma of Head and Neck/drug therapy, Survival",
author = "Jong-Mu Sun and Lin Shen and Shah, {Manish A} and Peter Enzinger and Antoine Adenis and Toshihiko Doi and Takashi Kojima and Jean-Philippe Metges and Zhigang Li and Sung-Bae Kim and Cho, {Byoung Chul} and Wasat Mansoor and Shau-Hsuan Li and Patrapim Sunpaweravong and Maqueda, {Maria Alsina} and Eray Goekkurt and Hiroki Hara and Luis Antunes and Christos Fountzilas and Akihito Tsuji and Oliden, {Victor Castro} and Qi Liu and Sukrut Shah and Pooja Bhagia and Ken Kato and {KEYNOTE-590 Investigators}",
note = "Copyright {\textcopyright} 2021 Elsevier Ltd. All rights reserved.",
year = "2021",
month = aug,
day = "28",
doi = "10.1016/S0140-6736(21)01234-4",
language = "English",
volume = "398",
pages = "759--771",
journal = "LANCET",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10302",

}

RIS

TY - JOUR

T1 - Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study

AU - Sun, Jong-Mu

AU - Shen, Lin

AU - Shah, Manish A

AU - Enzinger, Peter

AU - Adenis, Antoine

AU - Doi, Toshihiko

AU - Kojima, Takashi

AU - Metges, Jean-Philippe

AU - Li, Zhigang

AU - Kim, Sung-Bae

AU - Cho, Byoung Chul

AU - Mansoor, Wasat

AU - Li, Shau-Hsuan

AU - Sunpaweravong, Patrapim

AU - Maqueda, Maria Alsina

AU - Goekkurt, Eray

AU - Hara, Hiroki

AU - Antunes, Luis

AU - Fountzilas, Christos

AU - Tsuji, Akihito

AU - Oliden, Victor Castro

AU - Liu, Qi

AU - Shah, Sukrut

AU - Bhagia, Pooja

AU - Kato, Ken

AU - KEYNOTE-590 Investigators

N1 - Copyright © 2021 Elsevier Ltd. All rights reserved.

PY - 2021/8/28

Y1 - 2021/8/28

N2 - BACKGROUND: First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer.METHODS: We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment.FINDINGS: Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group.INTERPRETATION: Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population.FUNDING: Merck Sharp & Dohme.

AB - BACKGROUND: First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer.METHODS: We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment.FINDINGS: Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group.INTERPRETATION: Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population.FUNDING: Merck Sharp & Dohme.

KW - Antibodies, Monoclonal, Humanized/therapeutic use

KW - Antineoplastic Agents, Immunological/therapeutic use

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Cisplatin/therapeutic use

KW - Double-Blind Method

KW - Esophageal Neoplasms/drug therapy

KW - Female

KW - Fluorouracil/therapeutic use

KW - Humans

KW - Male

KW - Middle Aged

KW - Squamous Cell Carcinoma of Head and Neck/drug therapy

KW - Survival

U2 - 10.1016/S0140-6736(21)01234-4

DO - 10.1016/S0140-6736(21)01234-4

M3 - SCORING: Journal article

C2 - 34454674

VL - 398

SP - 759

EP - 771

JO - LANCET

JF - LANCET

SN - 0140-6736

IS - 10302

ER -