Overall survival (OS) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line (1L) FOLFIRINOX (FFX): Bridging the gap between the NAPOLI 3 trial and real-world practice.

690 Background: NALIRIFOX (liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin) demonstrated significantly improved OS compared to 1L gemcitabine + nab-paclitaxel in the phase 3 NAPOLI 3 trial (NCT04083235). The median OS (95% CI) in the NALIRIFOX intention-to-treat population (N= 383) was 11.1 (10.0, 12.1) months. However, the relative efficacy of NALIRIFOX versus FFX (irinotecan + 5-fluorouracil/leucovorin + oxaliplatin), another standard of care for 1L treatment of mPDAC, has not been studied. To further contextualize findings from NAPOLI 3 trial, the current study described OS among patients treated with 1L FFX in the real-world setting. Methods: Three cohorts of patients with mPDAC treated with 1L FFX were identified from the Flatiron Health database. The all-comer cohort included all adult patients with mPDAC treated with 1L FFX since January 2014. Among them, the trial-aligned cohort included patients with mPDAC treated with 1L FFX between January 1, 2020 and July 31, 2022 (to align with the time period of NAPOLI 3 trial) who met the eligibility criteria of NAPOLI 3. Finally, a subgroup of patients in the trial-aligned cohort who received modified FFX (mFFX) regimen composed the trial-aligned mFFX cohort. OS was assessed using Kaplan-Meier analysis. Results: The all-comer cohort consisted of 3,271 patients. The trial-aligned cohort included 219 patients, of whom 154 (70%) were treated with mFFX. The distribution of baseline characteristics was similar across three cohorts (Table). The median age of the trial-aligned cohort was 65 years old, with 46% of patients being female, 67% being White, and 47% having ECOG score of 1. The median OS (95% CI) in the all-comer cohort and trial-aligned cohort was 9.0 (8.5, 9.3) months and 9.1 (7.8, 10.9) months, respectively; the median OS (95% CI) was 8.6 (7.3, 10.5) months in the trial-aligned mFFX cohort. Conclusions: NALIRIFOX regimen in the NAPOLI 3 trial showed numerically improved OS compared to FFX, including mFFX, in the real-world setting. Analysis adjusting for baseline characteristics are warranted and will provide further insights for the comparative efficacy of the two regimens. Characteristics of real-world FOLFIRINOX cohorts. All-comer cohort(N=3,271) Trial-aligned cohort(N=219) Trial-aligned mFFX cohort (N=154) Baseline characteristics Age, years, mean (SD) 63.5 (9.0) 64.6 (8.2) 65.1 (8.5) Female, n (%) 1,377 (42.1) 100 (45.7) 68 (44.2) White, n (%) 2,118 (64.8) 146 (66.7) 100 (64.9) ECOG score = 1, n (%) 1,327 (48.9)* 103 (47.0) 77 (50.0) Endpoint Median OS, months (95% CI) 9.0 (8.5, 9.3) 9.1 (7.8, 10.9) 8.6 (7.3, 10.5) Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; OS, overall survival; SD, standard deviation. *Proportion calculated based on 2,711 patients with ECOG available at baseline.