FOLFIRINOX vs gem/pac in the elderly: Is the survival benefit worth the risk?

Abstract

e16420 Background: FOLFIRINOX (FFX) is standard first-line therapy for metastatic pancreatic adenocarcinoma (mPDAC) but is often avoided in elderly patients due to toxicity concerns, with Gemcitabine plus Nab-Paclitaxel (GP) frequently preferred. Comparative real-world data on survival and healthcare utilization (HCU) in elderly patients are limited. Methods: We performed a retrospective cohort study using the TriNetX Global Health Research Network. Patients aged ≥75 years with mPDAC treated with first-line FFX or GP through January 15, 2026 were identified. Propensity score matching (1:1 greedy nearest-neighbor, caliper 0.1) balanced baseline characteristics. Outcomes included 1-year overall survival (OS), 90-day safety events, and 90-day HCU. Subgroup analyses were performed for patients with CA19-9 > 1000 U/mL. Kaplan-Meier survival analysis and log-rank tests were used. Results: A total of 970 matched patients were included (485 per group). FFX was associated with improved 1-year OS compared with GP (57.1% vs 48.5%, p = 0.02). Median OS was not reached in the FFX group versus 11.7 months with GP. The hazard ratio for 1-year mortality favored FFX (HR 0.79; 95% CI 0.65–0.96) but was not statistically significant. No significant differences were observed in 90-day safety or HCU. Sepsis/septic shock occurred less frequently with FFX (8.2% vs 11.1%, p = 0.13). Hospitalization (35.3% vs 34.8%) and ICU admission (7.6% vs 5.8%) rates were similar. Among patients with CA19-9 > 1000, safety, HCU outcomes, and OS similarly favored FFX without increased toxicity. Conclusions: In elderly patients with mPDAC, first-line FOLFIRINOX was associated with improved survival without increased short-term toxicity or healthcare utilization, even among those with poor prognostic CA19-9 levels. These findings support FFX as a viable option for carefully selected elderly patients, though lack of functional status matching suggests possible selection of fitter individuals. Outcome FOLFIRINOX cohort (n=485) (purple) Gem/ Pac cohort (n= 485) (green) Hazard Ratio/ Risk Ratio (95% CI) p-value 1- year Overall Survival 0.79 (0.65 – 0.96) 0.66 Deceased 180 215 Survival Probability 57.1% 48.5% 0.02 Median Survival Not reached 11.7 months 90-day healthcare utilization Any hospitalization 171 (35.3%) 169 (34.8%) 1.012 (0.853, 1.201) 0.89 ICU admission 37 (7.6%) 28 (5.8%) 1.321 (0.822, 2.124) 0.25 90-daysafety outcomes Sepsis/ Severe Sepsis/ Septic shock 40 (8.2%) 54 (11.1%) 0.741 (0.502, 1.093) 0.13 Survivability CA19-9>1000 U/ml cohort FOLFORNIOX(n 109) 1 year survival %: 60.1 Gem/Pac (n 109) 1 year survival %: 44.3% **Hazard ratio 0.64 (0.43-0.95) 0.024