Efficacy and safety of FOLFIRINOX versus gemcitabine-based regimens in locally advanced pancreatic carcinoma: A systematic review and meta-analysis.

Abstract

e16391 Background: Locally advanced pancreatic cancer (LAPC) is often unresectable due to vascular involvement, and systemic therapy is the treatment backbone with the goal of improving survival and, in selected patients, enabling resection. FOLFIRINOX is commonly used in fit patients, but its comparative benefit over gemcitabine-based regimens in LAPC remains uncertain. We conducted a systematic review and meta-analysis to compare efficacy and safety of these approaches in LAPC. Methods: We searched PubMed, Embase, Scopus, CENTRAL, and ClinicalTrials.gov for randomized controlled trials and comparative cohort studies in adults with LAPC evaluating FOLFIRINOX versus gemcitabine-based regimens (including nab-paclitaxel). Random-effects meta-analysis pooled hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS), and risk ratios (RR) for response, progression, resection, and grade ≥3 hematologic toxicity. Subgroup analyses were performed by comparator regimen. Results: Six comparative studies (n = 1,766) were included. Overall survival (OS) favored FOLFIRINOX but did not reach statistical significance (HR 0.81; 95% CI 0.66–1.01; p = 0.06; I² = 45). Progression free survival (PFS) showed no significant difference (HR 1.11; 95% CI 0.79–1.54; p = 0.55; I² = 60%). There were no significant differences in objective response (RR 1.07; 95% CI 0.79–1.47; p = 0.65; I² = 38%), disease control (RR 1.13; 95% CI 0.99–1.30; p = 0.08; I² = 0%), progressive disease (RR 0.82; 95%CI 0.43–1.56; p = 0.54; I² = 55%), or resection rate (RR 1.03; 95% CI 0.57–1.86; p = 0.91; I² = 0%). Grade ≥3 neutropenia was higher with FOLFIRINOX (RR 2.21; 95% CI 1.21–4.04; p = 0.01; I² = 49%), as was febrile neutropenia (RR 4.26; 95% CI 1.78–10.17; p = 0.001; I² = 0%) with consistent findings in subgroup analyses. Conclusions: In LAPC, FOLFIRINOX showed borderline, non-significant improvement in overall survival and no improvement in progression-free survival. Response, disease control, progression, and resection outcomes were similar between regimens. FOLFIRINOX increased the risk of grade ≥3 neutropenia and febrile neutropenia. Treatment selection should be individualized based on patient fitness and toxicity risk, and perspective comparative studies are needed.