{"entity":{"id":"espac-4","kind":"trial","name":"ESPAC-4","aka":["ESPAC4"],"tldr":"ESPAC-4 showed that adding the tablet capecitabine to gemcitabine after pancreatic cancer surgery lengthened median survival from 25.5 to 28 months, and the pair became the adjuvant standard for people who cannot tolerate the harsher FOLFIRINOX regimen.","summary":"ESPAC-4 was an open-label phase 3 trial of the European Study Group for Pancreatic Cancer at 92 hospitals, randomising 730 analysed patients with resected pancreatic ductal adenocarcinoma to six cycles of gemcitabine or gemcitabine with capecitabine. The primary endpoint was overall survival.\n\nMedian overall survival was 28.0 months with the combination against 25.5 months with gemcitabine alone (hazard ratio 0.82), with 608 grade 3 to 4 adverse events in 226 patients on the combination against 481 in 196 patients on gemcitabine. The combination became a standard adjuvant option, later placed behind modified FOLFIRINOX (PRODIGE 24) for fit patients, which is how the corpus's resectable pancreatic cancer page cites it. The trial is registered only with the ISRCTN registry.","status":"positive","asOf":"2026-09-22","links":[{"label":"ISRCTN96397434","url":"https://www.isrctn.com/ISRCTN96397434"},{"label":"Palmer et al., ESPAC4 long-term outcomes (JCO 2025)","url":"https://doi.org/10.1200/JCO.24.01118"},{"label":"NICE NG85 recommendation 1.8.6","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":["soc-trials"],"related":[],"cancers":["resectable-pdac","pancreatic"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["gemcitabine","capecitabine"],"companies":[],"institutions":["liverpool-hpb-centre"],"pathways":[],"terms":["pancreatic-cancer-uk-drug-access"],"trials":["prodige-24","apact","jaspac-01"],"people":["paula-ghaneh","daniel-palmer"],"bottlenecks":[],"keyPapers":["paper-espac-4-gemcitabine-capecitabine-adjuvant-pancreatic-lancet-2017"],"journals":[],"dependsOn":[],"notes":["Long-term outcomes (JCO 2025, Palmer et al.; median follow-up 104 months, 566 deaths): median overall survival 31.6 months with gemcitabine plus capecitabine against 28.4 months with gemcitabine (hazard ratio 0.83, 0.71 to 0.98; p 0.031); after R0 resection 49.9 against 32.2 months (hazard ratio 0.63; p 0.002); five-year survival in node-negative patients 59 against 53 percent (hazard ratio 0.63; p 0.04) with no significant difference in node-positive patients; the 193 patients (26.4 percent) who would not have been eligible for PRODIGE 24 still benefited (25.9 against 20.7 months, hazard ratio 0.71; p 0.038). The authors conclude gemcitabine plus capecitabine is the standard for people not eligible for modified FOLFIRINOX, which is NICE NG85's recommendation 1.8.6 for England."],"nct":"ISRCTN96397434","phase":"3","setting":"Resected pancreatic ductal adenocarcinoma within 12 weeks of surgery in the United Kingdom, Germany, France and Sweden: six cycles of adjuvant gemcitabine alone against gemcitabine plus capecitabine, with overall survival as the primary endpoint","sponsor":"University of Liverpool (Cancer Research UK)","result":"Median overall survival 28.0 months with gemcitabine plus capecitabine against 25.5 months with gemcitabine alone (hazard ratio 0.82, p 0.032).","yearReported":2017,"enrolled":732,"enrolledBasis":"registered","enrolledNote":"ESPAC-4 has no ClinicalTrials.gov record; the figure is the 732 enrolled in the Lancet report, of whom 730 were analysed (366 gemcitabine, 364 gemcitabine plus capecitabine); the trial is registered as ISRCTN96397434.","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Adjuvant gemcitabine + capecitabine","n":364,"value":28,"note":"95% CI 23.5 to 31.5"},{"name":"Adjuvant gemcitabine","n":366,"value":25.5,"note":"95% CI 22.7 to 27.9"}],"hr":0.82,"ci":[0.68,0.98],"p":"0.032","source":"https://doi.org/10.1016/S0140-6736(16)32409-6"},{"endpoint":"Patients with grade 3 to 4 adverse events","unit":"%","arms":[{"name":"Adjuvant gemcitabine + capecitabine","n":359,"value":63,"note":"226 of 359 patients, 608 events"},{"name":"Adjuvant gemcitabine","n":366,"value":54,"note":"196 of 366 patients, 481 events"}],"source":"https://doi.org/10.1016/S0140-6736(16)32409-6"},{"endpoint":"Overall survival, long-term follow-up (median 104 months)","unit":"months","arms":[{"name":"Adjuvant gemcitabine + capecitabine","n":365,"value":31.6,"note":"95% CI 26.5 to 38.0"},{"name":"Adjuvant gemcitabine","n":367,"value":28.4,"note":"95% CI 25.2 to 32.0"}],"hr":0.83,"ci":[0.71,0.98],"p":"0.031","source":"https://doi.org/10.1200/JCO.24.01118"},{"endpoint":"Overall survival after R0 resection (long-term)","unit":"months","arms":[{"name":"Adjuvant gemcitabine + capecitabine","value":49.9,"note":"95% CI 39.0 to 82.3"},{"name":"Adjuvant gemcitabine","value":32.2,"note":"95% CI 27.9 to 41.6"}],"hr":0.63,"ci":[0.47,0.84],"p":"0.002","source":"https://doi.org/10.1200/JCO.24.01118"}]},"route":"/trials/espac-4/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"}],"institution":[{"id":"liverpool-hpb-centre","kind":"institution","name":"Liverpool University Hospitals HPB centre (Aintree)","route":"/institutions/liverpool-hpb-centre/"}],"term":[{"id":"pancreatic-cancer-uk-drug-access","kind":"term","name":"Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)","route":"/terms/pancreatic-cancer-uk-drug-access/"}],"trial":[{"id":"apact","kind":"trial","name":"APACT","route":"/trials/apact/"},{"id":"conko-001","kind":"trial","name":"CONKO-001","route":"/trials/conko-001/"},{"id":"espac-1","kind":"trial","name":"ESPAC-1","route":"/trials/espac-1/"},{"id":"jaspac-01","kind":"trial","name":"JASPAC 01","route":"/trials/jaspac-01/"},{"id":"prodige-24","kind":"trial","name":"PRODIGE 24 / CCTG PA6","route":"/trials/prodige-24/"}],"person":[{"id":"daniel-palmer","kind":"person","name":"Daniel Palmer","route":"/people/daniel-palmer/"},{"id":"paula-ghaneh","kind":"person","name":"Paula Ghaneh","route":"/people/paula-ghaneh/"}],"paper":[{"id":"paper-espac-4-gemcitabine-capecitabine-adjuvant-pancreatic-lancet-2017","kind":"paper","name":"ESPAC-4: adjuvant gemcitabine plus capecitabine versus gemcitabine alone after resection of pancreatic cancer","route":"/key-papers/paper-espac-4-gemcitabine-capecitabine-adjuvant-pancreatic-lancet-2017/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}]}}