671OConversion rate in locally advanced pancreatic cancer (LAPC) after nab-paclitaxel/gemcitabine- or FOLFIRINOX-based induction chemotherapy (NEOLAP): Final results of a multicenter randomised phase II AIO trial

Abstract Background The optimal preoperative treatment for LAPC is unknown. This first prospective, randomised trial was designed to compare the efficacy and safety of nab-Paclitaxel and Gemcitabine (nPG) with Fluorouracil, Leucovorin, Irinotecan, Oxaliplatin (FOLFIRINOX) as induction chemotherapy in LAPC. Methods In this open-label, randomised, two-arm, phase 2 trial, treatment-naive patients (pts) with histologically/cytologically proven non-resectable LAPC were recruited from 33 German centres. After two cycles of nPG induction pts without progressive disease or unacceptable adverse events were randomly allocated (1:1) to receive either two additional cycles of nPG or four cycles of sequential un-modified sqFOLFIRINOX. Secondary resectability was assessed by surgical exploration in all pts with at least stable disease (SD) after completion of induction chemotherapy. The primary endpoint was conversion rate (R0/R1 resection). Secondary endpoints included overall survival (OS) and safety. Results 168 pts were registered and 130 were randomly allocated (64 to nPG and 66 to sqFOLFIRINOX). Disease control rate (DCR) after randomization was 82.3% in the nPG group and 75.0% % in the sqFOLFIRINOX group. Surgical exploration was performed in 62.5% of randomized pts in the nPG group and 63.6% in the sqFOLFIRINOX group. The conversion rate as primary endpoint was 30.6% in the nPG group and 45.0% in the sqFOLFIRINOX group (Odds ratio 0.54; 95% CI, 0.26 to 1.13; P = 0.135). At a median follow-up of 12.9 months, the median overall survival was 17.2 months in the nPG group and 22.5 months in the sqFOLFIRINOX group (adjusted Hazard ratio 0.73; 95% CI, 0.42 to 1.28; P = 0.268). Among all intention-to-treat pts (N = 165) conversion was associated with significant improved overall survival (27.4 vs. 14.2 months; P = 0.0035). Adverse events of ≥ grade 3 occurred in 54.7% of the patients in the the nPG group and in 53.0% of those in the in the sqFOLFIRINOX group. Conclusions Secondary resection after 4 months of induction combination chemotherapy followed by surgical exploration is feasible in about a third of pts with LAPC and associated with prolonged survival. Clinical trial identification NCT02125136; 2013-004796-12. Legal entity responsible for the study AIO-Studien-gGmbH. Funding Celgene. Disclosure V. Kunzmann: Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (institution): Servier; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. H. Algul: Honoraria (self): Celgene; Honoraria (self): Servier; Research grant / Funding (self): Chugai. E. Goekkurt: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Travel / Accommodation / Expenses: Servier. U.M. Martens: Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Roche. D. Waldschmidt: Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene. U. Pelzer: Advisory / Consultancy, Research grant / Funding (institution): Celgene. J. Siveke: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Roche. F. Kullmann: Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene. S. Boeck: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene. T.J. Ettrich: Research grant / Funding (institution): Shire; Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Ipsen. All other authors have declared no conflicts of interest.