Background: The NAPOLI-1 study, a randomized phase 3 study in pts with mPDAC previously treated with gemcitabine-based therapy, demonstrated an improvement in overall survival (OS) with liposomal irinotecan + 5-fluorouracil/ leucovorin (5-FU/LV) vs. 5-FU/LV. In this analysis we describe the trends in pt characteristics, real-world OS (rwOS), and real-world time to-treatment failure (rwTTF) among pts with mPDAC treated with liposomal Irinotecan based regimens overall and stratified by tx initiation prior to 2018 (pre-2018) or after 2018 (post-2018). Methods: This retrospective observational study used de-identified data from Flatiron Health EHR database from over 280 cancer clinics in the US. Pt characteristics, rwOS, and rwTTF were assessed in adult pts diagnosed with mPDAC who received liposomal irinotecan treatment (tx) between January 1, 2016 and October 31, 2019. Results: Of the 590 pts treated with liposomal irinotecan based regimens, 53% were male, 56% were initially diagnosed with Stage IV disease, 92% were treated in the community setting, and median age at tx initiation was 69 (IQR: 62 – 75) years. Among pts with available ECOG scores (N = 435), 77% had a score of 0 or 1. 43% (n = 254) initiated tx pre-2018 and 57% (n = 336) post-2018. Pre-2018, 106 (42%) pts initiated liposomal irinotecan in the third line metastatic setting or later (3rd line+), 125 (49%) had ECOG score of 0-1, and median age was 68 (62–74) years. Post-2018, 36% of pts initiated tx in 3rd line+, 211 (63%) had ECOG score of 0-1, and median age was 70 (63 – 75) years. Median rwOS was 4.4 months [95% CI: 4.3–6.2] pre-2018 and 5.2 mos [4.3–6.2] post-2018. rwTTF was 1.6 mos [1.4–1.9] pre-2018 and 2.1 mos [1.6–2.5] among pts post-2018. Among pts treated in first- or second-line, pre-2018 rwOS was 5.3 mos [3.9–6.4] and post-2018 rwOS was 6.3 mos [5.0– 7.6]. Conclusions: In this descriptive real-world study of pts with mPDAC receiving liposomal irinotecan based regimens, pts initiating treatment post-2018 appear to be less pre-treated, older, and have better performance status than pts pre-2018. Pts treated post-2018 experienced numerically longer rwTTF and rwOS than pts treated pre-2018.