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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.
Background: 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. 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 overall survival; secondary endpoints were toxicity, relapse free survival, 2 and 5 year survival and quality of life. 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, 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. The data freeze was on March 2 2016. 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. Stratified log-rank analysis revealed an HR=0.82 [95% CI, 0.68 – 0.98]; χ2 (1) = 4.61, P=0.032. 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). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: ISRCTN96397434.
Abstracts by John P. Neoptolemos:
PET-PANC: Multi-centre prospective diagnostic accuracy and clinical value trial of FDG PET/CT in the diagnosis and management of suspected pancreatic cancer.Meeting: 2016 ASCO Annual Meeting | Abstract No: 4008
Predictive cytokine biomarkers for survival in patients with advanced pancreatic cancer randomized to sequential chemoimmunotherapy comprising gemcitabine and capecitabine (GemCap) followed by the telomerase vaccine GV1001 compared to concurrent chemoimmunotherapy in the TeloVac phase III trial.Meeting: 2014 ASCO Annual Meeting | Abstract No: 4121
Presentations by John P. Neoptolemos:
Ampullary cancer ESPAC-3 (v2) trial: A multicenter, international, open-label, randomized controlled phase III trial of adjuvant chemotherapy versus observation in patients with adenocarcinoma of the ampulla of vater.Meeting: 2011 ASCO Annual Meeting Abstract No: LBA4006Session: Gastrointestinal (Noncolorectal) Cancer (Oral Abstract Session)
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 AdenocarcinomaMeeting: 2016 ASCO Annual Meeting Abstract No: LBA4006Session: Gastrointestinal (Noncolorectal) Cancer (Oral Abstract Session)