{"entity":{"id":"keynote-590","kind":"trial","name":"KEYNOTE-590","aka":[],"tldr":"Added immunotherapy to first-line chemotherapy for all types of oesophageal cancer, with a survival benefit that held at five years.","summary":"KEYNOTE-590, trial NCT03189719 sponsored by Merck and reported in 2020, added pembrolizumab to first-line cisplatin and fluorouracil chemotherapy for all types of advanced oesophageal cancer and Siewert type I junction tumours, with a survival benefit that held at five years. It randomised 749 patients and met its primary overall survival endpoint in all patients, with a larger effect in PD-L1 CPS 10 or higher, and the five-year follow-up published in ESMO Open in 2025 confirmed the benefit; the FDA approved it for all patients in March 2021 while the EMA restricted it to CPS 10 or higher. OnCo links it to oesophageal cancer, PD-1 as a target, pembrolizumab, the CPS term and Ken Kato. Benefit in PD-L1-negative disease is uncertain, which is the open question behind the regional label split.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03189719","url":"https://clinicaltrials.gov/study/NCT03189719"}],"tags":[],"related":[],"cancers":["esophageal","oesophageal-squamous-cell-carcinoma","oesophageal-adenocarcinoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["cps"],"trials":[],"people":["ken-kato"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03189719","phase":"3","setting":"First-line advanced oesophageal cancer (squamous and adenocarcinoma) and Siewert I GEJ: pembrolizumab + cisplatin/5-FU vs chemotherapy","sponsor":"Merck","result":"OS 12.4 vs 9.8 months (HR 0.73); 5-year OS HR 0.72.","started":"2017-07-25","startedType":"actual","yearReported":2020,"enrolled":749,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, all patients","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","n":373,"value":12.4},{"name":"Placebo + chemotherapy","n":376,"value":9.8}],"hr":0.73,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01234-4/abstract"},{"endpoint":"Overall survival at 5-year follow-up","arms":[{"name":"Pembrolizumab + chemotherapy"},{"name":"Placebo + chemotherapy"}],"hr":0.72,"ci":[0.62,0.84],"source":"https://www.esmoopen.com/article/S2059-7029(25)01723-5/fulltext"}],"replication":"Replicated by CheckMate 648, RATIONALE-306, ESCORT-1st, JUPITER-06, and ORIENT-15 in squamous disease."},"route":"/trials/keynote-590/","neighbours":{"cancer":[{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","route":"/cancers/oesophageal-adenocarcinoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"oesophageal-squamous-cell-carcinoma","kind":"cancer","name":"Oesophageal squamous cell carcinoma","route":"/cancers/oesophageal-squamous-cell-carcinoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"}],"person":[{"id":"ken-kato","kind":"person","name":"Ken Kato","route":"/people/ken-kato/"}],"paper":[{"id":"paper-keynote-590-lancet-2021","kind":"paper","name":"KEYNOTE-590: pembrolizumab plus chemotherapy for first-line treatment of advanced oesophageal cancer","route":"/key-papers/paper-keynote-590-lancet-2021/"}]}}