Title: 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

Neoptolemos, J.P. et al.


What You Need to Know:

Results of a phase 3 study demonstrated that combination therapy with gemcitabine plus capecitabine increased overall survival compared to gemcitabine monotherapy in patients who had recently undergone resection for pancreatic cancer.

Trial Design:

  • Open-label, multicenter, phase 3 randomized clinical trial evaluated the safety and efficacy of gemcitabine plus capecitabine versus gemcitabine alone in patients with resected pancreatic cancer
  • Patients included were 18 years old who had “undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection)”
  • Patients were randomly assigned (1:1) to receive 6 cycles of gemcitabine alone (1 cycle = 1000 mg/m2 administered once weekly for 3 of every 4 weeks) or with oral capecitabine (1 cycle = 1660 mg/m2 given for 21 days, then 7 days without medication) within 12 weeks of surgery
  • Primary endpoint: overall survival (measured as the duration of time from randomization to death due to any cause); analyzed in the intention-to-treat population
  • Safety evaluated in all patients who received treatment

Key Outcomes:

  • 366 patients received gemcitabine monotherapy, 364 patients received gemcitabine + capecitabine
  • “The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths”
  • Median overall survival: 28.0 months for gemcitabine + capecitabine patients (95% CI: 23.5, 31.5) vs 25.5 months for gemcitabine patients (95% CI: 22.7, 27.9) (HR: 0.82; 95% CI: 0.68, 0.98; P=0.032)
  • Grade 3-4 adverse events: 226 of the 359 gemcitabine + capecitabine patients reported a total of 608 adverse events vs 196 of the 366 gemcitabine patients, who reported a total of 481 adverse events