Overall survival and treatment-related outcomes with FOLFIRINOX compared with gemcitabine/nab-paclitaxel in metastatic pancreatic cancer.

Abstract

e16436 Background: FOLFIRINOX and gemcitabine plus nab-paclitaxel are commonly used first-line regimens for metastatic pancreatic ductal adenocarcinoma (mPDAC). While randomized trials have demonstrated survival advantages with FOLFIRINOX, real-world comparative effectiveness and toxicity data remain limited. We compared survival and clinically relevant outcomes between these regimens in routine clinical practice. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults with mPDAC treated with FOLFIRINOX (cohort 1) or gemcitabine/nab-paclitaxel (cohort 2). The index date was first treatment administration. Outcomes were assessed from 1 to 365 days. Propensity score matching (1:1) was performed to balance demographics, comorbidities, and baseline laboratory values. The primary outcome was overall survival (OS). Secondary outcomes included hospitalization, emergency department (ED) visits, neutropenia, ERCP utilization, transaminitis, venous thromboembolism (DVT/PE), granulocyte colony-stimulating factor (G-CSF) use, and neuropathy. Time-to-event analyses used Kaplan–Meier methods with log-rank testing and Cox proportional hazards models. Results: After propensity score matching, 2,364 patients were included (1,182 per cohort) with well-balanced baseline characteristics. Median OS was significantly longer with FOLFIRINOX compared with gemcitabine/nab-paclitaxel (239 vs 164 days). Kaplan–Meier analysis demonstrated superior survival with FOLFIRINOX (log-rank p < 0.001), corresponding to a 25% reduction in mortality (HR 0.75, 95% CI 0.67–0.84). No significant differences were observed in hospitalization (log-rank p = 0.867; HR 1.01, 95% CI 0.91–1.12), ED visits (log-rank p = 0.754; HR 1.02, 95% CI 0.90–1.16), ERCP utilization (log-rank p = 0.606; HR 1.08, 95% CI 0.81–1.43), transaminitis (log-rank p = 0.305; HR 1.30, 95% CI 0.79–2.16), DVT/PE (log-rank p = 0.457; HR 0.93, 95% CI 0.78–1.12), or neuropathy (log-rank p = 0.464; HR 1.08, 95% CI 0.89–1.30). G-CSF use was significantly higher with FOLFIRINOX (log-rank p < 0.001; HR 2.50, 95% CI 2.10–2.99). Conclusions: In this large real-world analysis, FOLFIRINOX was associated with significantly improved overall survival compared with gemcitabine/nab-paclitaxel in metastatic pancreatic cancer, without increased hospitalization or most toxicity-related outcomes, though with greater hematologic support requirements. These findings provide real-world confirmation of clinical trial data and inform treatment selection in routine practice.