AbstractBackgroundSubgroup analyses of the NAPOLI‐1 study identified that among patients who were irinotecan naïve prior to entering the clinical trial, a survival benefit was observed between the study arm and control arm. This treatment benefit was not observed among those previously exposed to irinotecan. This study sought to understand the impact of prior exposure to irinotecan on clinical outcomes among patients treated with liposomal irinotecan in the real‐world setting.MethodsThis retrospective observational study utilized a nationwide electronic health record (EHR)‐derived deidentified database. Data for adult patients with mPDAC treated with liposomal irinotecan‐based regimens between January 2016 and October 2020 were analyzed. Patient characteristics, overall survival (OS), and progression‐free survival (PFS) were assessed. Cox proportional hazard methods were used to calculate hazard ratios (HRs). HRs were adjusted for demographics and relevant clinical covariates.ResultsSix hundred and seventy‐five patients with mPDAC treated with a liposomal irinotecan‐based regimen were included. The unadjusted OS HR was 1.3 (95% CI: 1.1–1.6,p< 0.001) and unadjusted PFS was HR 1.4 (95% CI: 1.2–1.7,p< 0.001). After adjustment for baseline characteristics, the adjusted OS HR was 1.0 (95% CI: 0.8–1.3,p= 0.8836) and the adjusted PFS HR was 1.1 (95% CI: 0.8–1.4,p= 0.5626).ConclusionsPrior irinotecan was not found to be a significant predictor of patient outcomes in those later treated with liposomal irinotecan. Thus, the results may inform the rationale for utilizing liposomal irinotecan combination therapy following prior irinotecan exposure in mPDAC, in particular where the prior irinotecan exposure was more distant in time.