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: Five year follow-up.

Abstract

4516 Background: The ESPAC-4 trial demonstrated that adjuvant GEM/CAP for pancreatic cancer significantly improved survival compared to GEM monotherapy. The aim of this study is to evaluate the long-term outcomes in the ESPAC-4 trial. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4-week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was five-year survival; secondary endpoints were toxicity and relapse free survival. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2-year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 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, 61% were R1 resections, 80% were node positive and 40% were poorly differentiated. The data freeze was on 24 February 2020; median follow up was 60 months with 531 overall deaths, 280 in GEM, and 251 in GEM/CAP. Median (95% CI) survival (months) for patients treated with GEM/CAP was 27.7 23.3 – 31.2) and 26.0 (22.7 – 28.4) for GEM. Five-year (95% CI) survival rates were 20 (16 – 25) % for GEM and 28 (23 – 33) % for GEM/CAP. Stratified log-rank analysis revealed an HR=0.84 [95% CI, 0.70 – 0.99]; χ2 (1) = 3.87, P=0.049. 70 out of 366 GEM patients in the safety set reported 101 grade 3/4 serious adverse events, while 65 out of 359 GEM/CAP patients reported 97 grade 3/4 serious adverse events ( P=0.724). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: 96397434 .