First-line Esophageal Carcinoma Study With Pembrolizumab Plus Chemo vs. Chemo (MK-3475-590/KEYNOTE-590)
Summary
The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally advanced or metastatic esophageal carcinoma. The overall primary efficacy hypotheses are as follows: 1. In participants with esophageal squamous cell carcinoma (ESCC), participants whose tumors are programmed cell death-ligand 1 (PD-L1)-positive (defined as combined positive score \[CPS\] ≥10), ESCC participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, overall survival (OS) is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy. 2. In participants with ESCC, participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy.
Timeline
- Start
- 2017-07-25
- Primary completion
- 2020-07-02
- Completion
- 2023-07-10
Outcome
Met primary endpoint
registry analysis (superiority test); Pembrolizumab + SOC vs Placebo + SOC; p <0.0001; Hazard Ratio (HR) 0.57 (95% CI 0.43 to 0.75); Stratified Log-Rank NCT03189719 ↗
registry analysis (superiority test); Pembrolizumab + SOC vs Placebo + SOC; p = 0.0006; Hazard Ratio (HR) 0.72 (95% CI 0.60 to 0.88); Stratified Log-Rank NCT03189719 ↗
registry analysis (superiority test); Pembrolizumab + SOC vs Placebo + SOC; p <0.0001; Hazard Ratio (HR) 0.65 (95% CI 0.55 to 0.76); Stratified Log-Rank NCT03189719 ↗
Publications
- Kato K, Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, Yatsuzuka N, Sakata T, Han S, Doi T. First-line pembrolizumab plus chemotherapy versus chemotherapy alone for advanced esophageal cancer: 5-year extended follow-up in the Japanese subgroup of KEYNOTE-590. Esophagus. 2026 Apr 28. doi: 10.1007/s10388-026-01200-8. Online ahead of print.
- Zhang Y, Diez Garcia M, Shah S, Joo S, Valderrama A, Zhang S, Enzinger PC. Analysis of quality-adjusted survival time without symptoms or toxicity for pembrolizumab plus chemotherapy as treatment for previously untreated participants with advanced or metastatic esophageal cancer. Qual Life Res. 2026 Feb 1;35(3):58. doi: 10.1007/s11136-025-04109-4.
- Mansoor W, Joo S, Norquist JM, Kato K, Sun JM, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Sunpaweravong P, Alsina M, Goekkurt E, Suryawanshi S, Shah S, Shen L. Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer. Oncologist. 2024 Oct 3;29(10):e1324-e1335. doi: 10.1093/oncolo/oyae087.
- Kato K, Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, Ogata T, Ishihara R, Goto M, Baba H, Nishina T, Han S, Iwakami K, Yatsuzuka N, Doi T. First-line pembrolizumab plus chemotherapy for advanced/metastatic esophageal cancer: 1-year extended follow-up in the Japanese subgroup of the phase 3 KEYNOTE-590 study. Esophagus. 2024 Jul;21(3):306-318. doi: 10.1007/s10388-024-01053-z. Epub 2024 Apr 12.
- Zhang Y, Li C, Du K, Pengkhun N, Huang Z, Gong M, Li Y, Liu X, Li L, Wang D, Wang C, Chen F, Li J. Comparative analysis of immune checkpoint inhibitors in first-line treatment of esophageal squamous cell carcinoma: a network meta-analysis. Immunotherapy. 2023 Jul;15(10):737-750. doi: 10.2217/imt-2022-0236. Epub 2023 May 4.
- Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, Ogata T, Ishihara R, Goto M, Baba H, Nishina T, Han S, Sakata T, Yatsuzuka N, Doi T, Kato K. First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus. 2022 Oct;19(4):683-692. doi: 10.1007/s10388-022-00920-x. Epub 2022 Jun 7.
- Zhu Y, Liu K, Ding D, Zhou Y, Peng L. Pembrolizumab Plus Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A Cost-Effectiveness Analysis. Adv Ther. 2022 Jun;39(6):2614-2629. doi: 10.1007/s12325-022-02101-9. Epub 2022 Apr 8.
- Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, 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. 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. doi: 10.1016/S0140-6736(21)01234-4.
- Kato K, Shah MA, Enzinger P, Bennouna J, Shen L, Adenis A, Sun JM, Cho BC, Ozguroglu M, Kojima T, Kostorov V, Hierro C, Zhu Y, McLean LA, Shah S, Doi T. KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 2019 Apr;15(10):1057-1066. doi: 10.2217/fon-2018-0609. Epub 2019 Feb 8.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |
| Background | Cisplatin | Other / unclassified | 80 mg/m2 | Intravenous |
| Background | fluorouracil | Small molecule | 800 mg/m2 | Intravenous |