# ESPAC-4

Source: https://onco.cc/trials/espac-4/  
OnCo record `espac-4` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Median 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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-22
- Also known as: ESPAC4
- Tags: soc-trials
- Registry id: 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)
- Enrolled: 732
- 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).
- Outcomes: Overall survival: Adjuvant gemcitabine + capecitabine 28 months vs Adjuvant gemcitabine 25.5 months, HR 0.82; Patients with grade 3 to 4 adverse events: Adjuvant gemcitabine + capecitabine 63% vs Adjuvant gemcitabine 54%; Overall survival, long-term follow-up (median 104 months): Adjuvant gemcitabine + capecitabine 31.6 months vs Adjuvant gemcitabine 28.4 months, HR 0.83; Overall survival after R0 resection (long-term): Adjuvant gemcitabine + capecitabine 49.9 months vs Adjuvant gemcitabine 32.2 months, HR 0.63

## 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.

## Sources

- ISRCTN96397434: https://www.isrctn.com/ISRCTN96397434
- Palmer et al., ESPAC4 long-term outcomes (JCO 2025): https://doi.org/10.1200/JCO.24.01118
- NICE NG85 recommendation 1.8.6: https://www.nice.org.uk/guidance/ng85/chapter/Recommendations

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/)
- institutions: [Liverpool University Hospitals HPB centre (Aintree)](https://onco.cc/institutions/liverpool-hpb-centre/)
- terms: [Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)](https://onco.cc/terms/pancreatic-cancer-uk-drug-access/)
- trials: [APACT](https://onco.cc/trials/apact/), [CONKO-001](https://onco.cc/trials/conko-001/), [ESPAC-1](https://onco.cc/trials/espac-1/), [JASPAC 01](https://onco.cc/trials/jaspac-01/), [PRODIGE 24 / CCTG PA6](https://onco.cc/trials/prodige-24/)
- people: [Daniel Palmer](https://onco.cc/people/daniel-palmer/), [Paula Ghaneh](https://onco.cc/people/paula-ghaneh/)
- key papers: [ESPAC-4: adjuvant gemcitabine plus capecitabine versus gemcitabine alone after resection of pancreatic cancer](https://onco.cc/key-papers/paper-espac-4-gemcitabine-capecitabine-adjuvant-pancreatic-lancet-2017/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)

---
JSON: https://onco.cc/api/v1/entities/espac-4.json