A multi-institutional, single-arm, phase II trial of neoadjuvant modified-FOLFIRINOX for resectable pancreatic ductal adenocarcinoma.

Abstract

715 Background: Various peri-operative treatments have been tested to increase the survival of localized PDAC. Even with superior survival among various disease extent of PDAC, resectable PDAC still shows poor outcomes with surgery followed by adjuvant chemotherapy. We report the result of a multi-institutional phase II trial of modified-FOLFIRINOX as neoadjuvant treatment for resectable PDAC. Methods: Treatment naïve pts with histologically confirmed resectable PDAC were enrolled. Resectability was confirmed by both CT and MRI according to NCCN resectability criteria (no arterial tumor contact to celiac axis, SMA or CHA; no tumor contact with SMV or PV or ≤180° contact without vein contour irregularity) in multidisciplinary team meeting. Patients received oxaliplatin 85mg/m2 D1 + leucovorin 400mg/m2 D1 + irinotecan 150mg/m2 D1 + 5-FU 2,000mg/m2 46h continuous infusion, every other week for 6 cycles (12 weeks). Response assessments were performed every 6 weeks using the RECIST criteria version 1.1. Baseline MRI, PET-CT scan, and pre-surgery MRI after 6 cycles were mandatory. The primary endpoint was R0 resection rate. Secondary endpoints included survivals, ORR, safety, resection rate, and correlative biomarker exploration. (NCT05066802). Results: Total of 27 pts were enrolled between May 2020 and Feb 2022. Among total 27 pts, 24 pts underwent curative aim surgery after neoadjuvant treatment (resection rate 88.9%), and 23 pts showed R0 resection (23/27=85.2%), meeting the primary endpoint. Among 27 pts, 19 pts (70.4%) completed the neoadjuvant treatment per protocol. The reasons for neoadjuvant treatment discontinuation included progression of the disease (n=3, 11.1%) and pts withdrawal (n=5, 18.5%). Among 19 patients who underwent surgery per protocol, only one patient was R1 resected (R0 resection rate=94.7%). As of Sep 1, 2022 (median follow-up duration = 15.2 months) 6 pts recurred after surgery (6/19=31.6%). Median recur-free survival was 18.7 months (95%CI 13.6-NR) and median OS was not reached (95%CI 17.6-NR) for the per protocol treated pts. Treatment-related AE (≥G3) occurred in 10 pts (37.0%) including 7 (25.9%) with neutropenia G3-4. Conclusions: Three months of neoadjuvant mFOLFIRINOX was feasible and tolerable for resectable PDAC. Larger randomized trial is needed to validate the impact of neoadjuvant chemotherapy for resectable pancreatic cancer and to find subgroup of pts who would get benefit most from the neoadjuvant treatment. Post hoc genomic analyses with paired pre-neoadjuvant treatment and surgical tissues are ongoing. Clinical trial information: NCT05066802 .