CHICAGO — Adjuvant gemcitabine plus capecitabine significantly improved overall survival compared with gemcitabine monotherapy in patients with pancreatic ductal adenocarcinoma, according to results of the ESPAC-4 trial presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.1
Calling the combination regimen “the new standard of care for resected pancreatic cancer,” John P. Neoptolemos, MD, PhD, University of Liverpool, Liverpool, United Kingdom, presenting on behalf of the European Study Group on Pancreatic Cancer (ESPAC), said the 5-year survival rate was “superior to previous ESPAC trial arms, including no chemotherapy, chemoradiotherapy, and 5FU/FA.”
Between January 2008 and September 2014, 722 patients were randomly assigned within 12 weeks of surgery to either six 4-week cycles of gemcitabine 1000 mg/m2 on days 1, 8, and 15 for 6 cycles alone (n = 366) or gemcitabine with oral capecitabine 1660 mg/m2/day for 21 days of a 28-day cycle (n = 364).
Median age was 65 years (range, 37 to 81 years) and 57% were men. Baseline WHO performance status was 0 (42%), 1 (55%), or 2 (3%), and postoperative median CA19-9 was 18.7 kU/L. Median maximum tumor size was 30 mm (range, 0-110); 60% were R1 resections, 80% were node positive, and 39% had poorly differentiated tumor grade.
“On December 11, 2015, the Independent Trial Steering Committee requested that the trial proceed to full analysis,” said Dr. Neoptolemos, and the data freeze occurred on March 2, 2016.
Results showed that median overall survival, the primary end point, for patients treated with gemcitabine plus capecitabine was 28.0 months (95% CI, 23.5-31.5) and 25.5 months (95% CI, 22.7-27.9) for gemcitabine alone (HR, 0.82; 95% CI, 0.68-0.98; χ2 (1) = 4.61, P = .032).
In the safety set, diarrhea was 19% in the gemcitabine/capecitabine arm vs 6% in the gemcitabine alone arm (P = .008); neutropenia was 38% vs 24% (P < .001); infections were 3% vs 7% (P = .012) and hand-foot syndrome was 7% vs 0% (P < .001).
Dr. Neoptolemos concluded by stating that “all patients with pancreatic cancer should be offered entry into randomized trials,” and that “biomarkers must be evaluated.”
1. Neoptolemos JP, Palmer D, Ghaneh P, et al. ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma. Oral presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.