AbstractBackgroundThe NAPOLI‐I trial showed better outcome of nanoliposomal irinotecan (nal‐IRI) plus 5‐fluorouracil/leucovorin (5‐FU/LV) compared to 5‐FU/LV in patients with advanced pancreatic ductal adenocarcinoma cancer (advPDAC) progressed to gemcitabine‐based therapy. This study aims to explore the real‐world efficacy and safety of 5‐FU/LV‐nal‐IRI.MethodsThis is a retrospective multicenter analysis including advPDAC patients receiving 5‐FU/LV‐nal‐IRI after failure of gemcitabine‐based therapy. Survival analyses were performed using Kaplan–Meier method, univariate and multivariate analyses by Cox regression.ResultsA total of 296 patients (median age 64.4 years, ECOG PS ≥1 in 56% of cases) were treated at 11 Italian institutions between 2016 and 2018. 34% of them underwent primary tumor resection, and 79% received gemcitabine‐nabpaclitaxel as first line. 5‐FU/LV‐nal‐IRI was administered as second‐line in 73% of cases.Objective response and disease control rate were 12% and 41%, respectively. Treatment was well tolerated with dose reductions in 50% of patients but no one permanent discontinuation; the commonest grade ≥3 toxicities were neutropenia (14%) and diarrhea (12%). Median PFS and OS from 5‐FU/LV‐nal‐IRI initiation was 3.2 and 7.1 months, respectively.ConclusionsThese real‐world data confirm the 5‐FU/LV‐nal‐IRI efficacy and safety in advPDAC patients progressed to gemcitabine‐based therapy, with outcomes comparable to NAPOLI‐1, even in a less‐selected population and with more modern therapeutic algorithm.