FOLFIRINOX vs. gemcitabine/nab-paclitaxel for metastatic pancreatic cancer: A real-world study

BACKGROUND: FOLFIRINOX and gemcitabine/nab-paclitaxel are widely used first-line regimens in metastatic pancreatic cancer (mPC); however, direct real-world comparisons and clear criteria for selecting between the two remain limited. METHODS: In this retrospective cohort study, we used a multicenter real-world data registry to compare outcomes between patients with mPC treated with FOLFIRINOX and gemcitabine/nab-paclitaxel and explore associations between genomic alterations and survival outcomes. The cohort included patients with mPC treated with FOLFIRINOX (n = 272) or gemcitabine/nab-paclitaxel (n = 280) between 2010 and 2022 at tertiary referral cancer centers. The primary outcomes were overall and progression-free survival. Available next-generation sequencing results were used to explore potential prognostic biomarkers. FINDINGS: The FOLFIRINOX group was significantly younger than the gemcitabine/nab-paclitaxel group. Before propensity score matching, the FOLFIRINOX group showed significantly longer median overall and progression-free survival. Afterward, survival outcomes no longer significantly differed. Next-generation sequencing panel data were available for 57 and 29 patients in the FOLFIRINOX and gemcitabine/nab-paclitaxel groups, respectively. In the gemcitabine/nab-paclitaxel group, ARID1A and RNF43 mutations were correlated with shorter progression-free survival. Genomic alterations in the TGF-β pathway were associated with longer overall survival with gemcitabine/nab-paclitaxel. INTERPRETATION: No statistically significant differences in OS or PFS were observed between FOLFIRINOX and gemcitabine/nab-paclitaxel after propensity score matching. The exploratory genomic associations require validation in larger prospective cohorts before their potential role in treatment selection can be established. FUNDING: This work was supported by grants from the National Research Foundation of Korea (RS-2024-00,335,625, RS-2024-00,342,475, and NRF-2021R1A2C1008898), Korea Evaluation Institute of Industrial Technology (20,023,781), and Korea Health Technology R&D Project through the Korea Health Industry Development Institute (HI22C047400).