ESPAC-4: An international randomized phase-3 trial of adjuvant combination chemotherapy using gemcitabine (GEM) and capecitabine (CAP) versus mono therapy gemcitabine in resected pancreatic cancer
Session type: Oral
The ESPAC-3 trial compared adjuvant GEM with 5-fluorouracil/folinic acid for resected pancreatic cancer. GEM is the standard of care based on similar survival and less toxicity. ESPAC-4 aimed to determine whether combination chemotherapy with GEM/CAP improved survival compared to GEM monotherapy.
Patients with pancreatic cancer were randomized to have either six 4wk cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was overall survival; secondary endpoints were toxicity, relapse free survival, 2 and 5 year survival and quality of life. The trial was designed to detect a hazard ratio of 0.74. Using a two-sided alpha level of 0.05, 480 events were required to obtain 90% power.
Between 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 60% were R1 resections, 80% were node positive and 40% were poorly differentiated. On Dec 11 2015 the Independent Trial Steering Committee requested that the trial proceed to full analysis. Stratified log-rank for overall survival produced an HR=0.82 [95% CI, 0.68 – 0.98]; χ2 (1) = 4.61, P=0.032. Median survival (months) for patients treated with GEM/CAP was 28.0 (95% CI, 23.5 – 31.5) and 25.5 (22.7 – 27.9) for GEM. The 5 year survival rate for the GEM/CAP was 28.8 (22.9 – 35.2) % and 16.3 (10.2 – 23.7) % for GEM. 196 out of 366 GEM patients in the safety set reported 481 grade 3/4 adverse events, while 226 out of 359 GEM/CAP patients reported 608 grade 3/4 adverse events (P=0.242).
Adjuvant GEM/CAP is the standard of care for resected pancreatic cancer.