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ESPAC-4

Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4)

Phase 3N = 732

Population
Adults with resected pancreatic ductal adenocarcinoma (R0 or R1); 732 enrolled, 730 in the final analysis.
Design
Open-label, multicentre randomised phase 3 trial at 92 hospitals in England, Scotland, Wales, Germany, France and Sweden. Patients aged 18 or older with complete macroscopic (R0 or R1) resection of pancreatic ductal adenocarcinoma were randomised 1:1 within 12 weeks of surgery to six cycles of gemcitabine 1000 mg/m2 weekly for three of every four weeks, with or without oral capecitabine 1660 mg/m2 for 21 days then 7 days rest. Minimisation with country as stratification factor. Primary endpoint overall survival in the intention-to-treat population. The independent data and safety monitoring committee requested reporting after 458 (95%) of a target 480 deaths. Registered as EudraCT 2007-004299-38 and ISRCTN96397434 (no NCT number).
Primary endpoint
OS
Arms
  • Gemcitabine (control, n = 366): Gemcitabine 1000 mg/m2 weekly for 3 of every 4 weeks, 6 cycles
  • Gemcitabine plus capecitabine (experimental, n = 364): Gemcitabine as in control plus oral capecitabine 1660 mg/m2 for 21 days then 7 days rest, 6 cycles
People
Neoptolemos JP
OSHR 0.82 (95% CI 0.68–0.98)Δ median OS+2.5 months
Show the numbers
Results reported for ESPAC-4
EndpointAnalysisGemcitabine plus capecitabineGemcitabineEffect
OSprimaryNeoptolemos 2017median 28 months (23.5–31.5)median 25.5 months (22.7–27.9)HR 0.82 (95% CI 0.68–0.98)P=0.032Reported at 458 deaths (95% of the 480 targeted) at the request of the independent data and safety monitoring committee; the abstract calls this the final analysis. Grade 3-4 adverse events: 226 of 359 patients with gemcitabine plus capecitabine and 196 of 366 with gemcitabine.
Results reported for ESPAC-4
EndpointAnalysisGemcitabine plus capecitabineGemcitabineEffect
OSprimaryNeoptolemos 2017median 28 months (23.5–31.5)median 25.5 months (22.7–27.9)HR 0.82 (95% CI 0.68–0.98)P=0.032Reported at 458 deaths (95% of the 480 targeted) at the request of the independent data and safety monitoring committee; the abstract calls this the final analysis. Grade 3-4 adverse events: 226 of 359 patients with gemcitabine plus capecitabine and 196 of 366 with gemcitabine.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.820.68–0.98
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%010203040506070Months (modelled)
  • Gemcitabine plus capecitabine (experimental)
  • Gemcitabine (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsGemcitabine plus capecitabineGemcitabine
0100.0%100.0%
1864.0%61.3%
3542.0%38.6%
5326.9%23.7%
7017.7%14.9%
Primary publication: Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011-1024. PubMedDOI

Appears in

Sources

  1. Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011-1024.

    PubMedDOI