Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)

Abstract Background mFOLFIRINOX and GEM are standard chemotherapy for pts with PDAC. This single-arm phase 2 trial assessed the efficacy and safety of perioperative chemotherapy consisted of preoperative mFOLFIRINOX and postoperative GEM in pts with BR/LA-PDAC. Methods Pts with histologically proven and radiologically confirmed BR/LA-PDAC as defined by NCCN criteria were eligible. Pts received 8 cycles of preoperative mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, 5-FU 2,400 mg/m2 over 46 hours, and leucovorin 400 mg/m2), every 2 weeks. For pts who underwent surgery, postoperative GEM (1,000 mg/m2 D1, 8, 15, every 4 weeks) was given for 6 cycles. Primary endpoint was 1-year progression-free survival (PFS) rate and secondary endpoints were PFS, overall survival (OS) and curative surgery rate. A total of 44 pts were required to show the improvement in 1-year PFS rates from 30% to 50% with a two-sided alpha of 0.05, beta of 0.8 and drop-out rates of 10%. Results Between May/2016 and Mar/2018, 44 patients were enrolled. Median age was 60 years (range, 35-76) and 26 pts (59%) were male. Pancreas head was most common site (n = 26, 59%), and 29 (66%) and 15 (34%) pts had BR- and LA-PDAC, respectively. With mFOLFIRINOX, response rate was 34% and surgery was done in 27 pts (61%); 22 and 5 pts achieved R0 and R1 resection, respectively, and postoperative GEM was given in 26 patients (96%). With median follow-up of 20.7 months (95% CI, 14.4-27.0), 1-year PFS rate was 52.0% (95% CI, 37.1-66.9), and 2-year OS rate was 49.8% (95% CI, 38.2-71.4). Median PFS and OS was 12.2 months (95% CI, 7.9-15.9), and 22.3 months (95% CI, 11.3-33.3), respectively. Median OS was significantly prolonged in pts who underwent surgery compared to those who did not (26.2 months [95% CI, 23.1-29.3] vs 9.0 months [95% CI, 6.6-11.4 months]; p  Conclusions Perioperative chemotherapy using mFOLFIRINOX and GEM was feasible and effective for pts with BR/LA-PDAC. Clinical trial identification NCT02749136. Legal entity responsible for the study The authors. Funding Boryung Pharmaceuticals. Disclosure All authors have declared no conflicts of interest.