Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable pancreatic ductal adenocarcinomas (BR-PDAC).

Abstract

342 Background: mFOLFIRINOX and GEM are standard chemotherapy for metastatic and resected PDAC, respectively. This phase 2 trial assessed the efficacy and safety of perioperative chemotherapy consisted of preoperative mFOLFIRINOX and postoperative GEM in pts with BR-PDAC. Methods: Pts with histologically proven and radiologically confirmed BR-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%). With mFOLFIRINOX, response rate was 34% and surgery was done in 27 patients (61%); 22 and 5 patients achieved R0 and R1 resection, respectively, and postoperative GEM was given in 24 patients (89%). With median follow-up of 16.6 months (95% CI, 10.9-22.2), 1-year PFS rate was 51.7% (95% CI, 35.2-68.2), and median PFS and OS was 13.0 months (95% CI, 7.7-18.4), and 14.3 months (95% CI, not available), respectively. PFS and OS were significantly differed according to the surgery (p < 0.001 for both) and response to mFOLFIRINOX (p < 0.001 and p = 0.03, respectively). Relative dose intensities of irinotecan, oxaliplatin and 5-FU were > 77% during mFOLFIRINOX. Grade 3-4 neutropenia (55%), anemia (14%), nausea (11%), and diarrhea (7%) were most common severe toxicities and 3 pts (7%) discontinued mFOLFIRINOX due to the toxicities. Conclusions: Perioperative chemotherapy using mFOLFIRINOX and GEM were feasible and effective for pts with BR-PDAC. Future randomized trial is warranted. Clinical trial information: NCT02749136.