Effectiveness, safety, and patient-reported quality of life with first-line chemotherapy in advanced pancreatic cancer: A nationwide prospective multicenter observational study.

e16388 Background: In advanced pancreatic cancer, mFOLFIRINOX and gemcitabine plus nab-paclitaxel (GnP) are commonly used as first-line chemotherapy options, while it remains unclear which regimen provides superior clinical outcomes. We conducted a prospective real-world observational study to evaluate factors influencing first-line treatment selection and associated effectiveness and quality-of-life outcomes. Methods: This prospective, multicenter observational study enrolled patients with advanced pancreatic cancer initiating first-line palliative chemotherapy at 25 centers in Korea between January 2021 and June 2024, with follow-up of up to 12 months. First-line regimens were selected at investigators’ discretion, and factors related to treatment selection were prospectively collected. The primary endpoint was progression-free survival (PFS) assessed by investigator review per RECIST v1.1; secondary endpoints included overall survival (OS), safety, and quality of life assessed using FACT-Hep at baseline, 2 months, and 6 months. Results: A total of 799 patients were enrolled, of whom 787 were eligible for the final analysis. First-line regimens included mFOLFIRINOX (n = 423), GnP (n = 332), and gemcitabine monotherapy (n = 32). Selection of first-line therapy was primarily influenced by ECOG performance status (39.1%) and age (26.2%), with a higher proportion of patients aged ≤65 years receiving mFOLFIRINOX than GnP (52% vs 27%). With a median follow-up of 10.7 months (IQR, 5.4–12.3), mFOLFIRINOX was associated with longer median PFS than GnP (7.1 vs 5.3 months; HR, 0.70; 95% CI, 0.6–0.9) and longer median OS (15.9 vs 10.1 months; HR, 0.60; 95% CI, 0.5–0.8), with similar trends observed in patients aged ≥65 years. Second-line palliative chemotherapy was administered in 39.5% of patients overall (42.6% with mFOLFIRINOX vs 37.4% with GnP). Grade ≥3 adverse events were more frequent with mFOLFIRINOX than with GnP (32.6% vs 22.6%), including higher rates of grade ≥3 neutropenia (19.4% vs 12.3%). FACT-Hep scores were maintained over time, with small increases in the mFOLFIRINOX group at 2 and 6 months (+2.2, +1.9) and slight decreases in the GnP group (−2.6, −1.5), suggesting relatively better quality-of-life preservation with mFOLFIRINOX. Conclusions: In this nationwide prospective real-world study, selection of first-line chemotherapy for advanced pancreatic cancer was driven primarily by patient age and performance status. mFOLFIRINOX was associated with more favorable effectiveness outcomes than GnP, without clinically meaningful deterioration in quality of life, even in older patients. As fewer than 40% of patients received second-line palliative chemotherapy, these findings underscore the importance of optimal first-line treatment selection and may inform routine clinical decision-making.