626PD - Randomized, phase III trial comparing adjuvant gemcitabine (Gem) versus Gem plus chemoradiation (CCRT) in curatively resected pancreatic ductal adenocarcinoma (PDAC): A Taiwan cooperative oncology group study

Abstract

Background: Adjuvant chemotherapy is the standard of care for PDAC after curative intent surgery. Current study aims to evaluate the role of additional consolidation CCRT to 6-month adjuvant Gem therapy in resectable PDAC. Methods: Patients with R0/R1 resected PDAC, and negative CT finding within 2 weeks and CA-19.9 <2.5x NUL within one week before registration were eligible. Enrolled patients were stratified by section margin, tumor size and lymph node status then randomized to have either 6 cycles of weekly gemcitabine, day 1, 8 and 15 every 28 days (Arm 1) or 3 cycles of weekly Gem followed by Gem-based CCRT and then another 3 cycles of Gem (Arm 2). The treatment should be initiated within 8 weeks after surgery. The primary end-point was recurrence-free survival (RFS). Secondary end points were overall survival (OS), progression pattern, safety profile and quality of life. Results: Between 2009 and 2015, 147 patients were included, 74 in Arm 1 and 73 in Arm 2. With a minimum of 2 years follow-up, the median RFS was similar between Arm 1 and Arm 2: 12.1(95% CI, 9·0-15·8) versus 13.3 (95% CI, 10.0-17.1) months, (hazard ratio 0.96 [95% CI, 0·67-1·37, p = 0.80]); while OS was 23·5 (95% CI, 18·1-30.8) versus 21·5 (95% CI, 16·7-28·1) months, (hazard ratio 1.07 [95% CI, 0·74-1·55, p = 0·73]). Local recurrence rate was marginally less in Arm 2 (17.6% vs 15.1%, p = 0·68). Grade 3/4 toxicity was 66% vs 73% in Arm 1 and 2, respectively, p = 0·34. Patients in Arm 1 had a trend of better global health status, p = 0·12. Conclusions: This is the first randomized trial using survival as primary endpoint to evaluate the role of add-on CCRT for curatively resected PDAC receiving standard, adjuvant Gem therapy. Despite a trend of better loco-regional control, the add-on CCRT did not improve the RFS and OS in such a patient population. Systemic chemotherapy should remain as the standard of care for PDAC after curative-intent surgery. Clinical trial identification: NCT00994721. Legal entity responsible for the study: Taiwan Cooperative Oncology Group. Funding: National Health Research Institutes. Disclosure: J-S. Chen: Research funding: Ono Pharmaceutical, MSD Oncology, MedImmune, Lilly, TTY Biopharm, Daiichi Sankyo, Orient EuroPharma. L-T. Chen: Research funding: Novartis, Merck, Serono, TTY, Polaris, SyncorePharm, Pfizer, BMS; Honoraria: Ono, Eli Lilly, MSD, PharmaEngine, TTY, SyncorePharm, Novartis, Astra Zeneca, Ipsen; Patents & Royalties of ENO-1mAb/HuniLife; Membership on board of directors or advisory committes: PharmaEngine. All other authors have declared no conflicts of interest.