Efficacy and safety of FOLFIRINOX versus gemcitabine-based regimens for treatment of metastatic pancreatic cancer: A systematic review and meta-analysis.

Abstract

e16393 Background: Metastatic pancreatic cancer (MPC) is an aggressive malignancy with limited treatment options. FOLFIRINOX, a combination regimen of folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin offers improved survival but with higher toxicity. In contrast, gemcitabine-based therapies remain the standard of care due to their manageable safety profile. This meta-analysis evaluates the efficacy and safety of these regimens to guide optimal MPC treatment strategies. Methods: A systematic review was conducted across six databases -- PubMed (MEDLINE), Google Scholar, ScienceDirect, PLOS ONE, Cochrane Library, and ClinicalTrials.gov-- up to January 17 2025. Thirteen retrospective studies and three randomized controlled trials (RCTs) were included, limited to Human studies in English. Bias was assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool. Data analysis was performed using RevMan 5.4. Results: FOLFIRINOX-treated patients (n = 3,020) demonstrated significantly longer overall survival (OS) than gemcitabine-treated patients (n = 3,693), with a mean difference of 2.82 months (95% CI: 2.74–2.89; P < 0.00001). Progression-free survival (PFS) showed a smaller, non-significant difference of 0.18 months (95% CI: -0.09–0.46; P = 0.19). Severe neutropenia occurred significantly more frequently in the FOLFIRINOX group (n = 2,034) compared to gemcitabine-treated patients (n = 2,239), with an Odds Ratio of 1.49 (95% CI: 1.27–1.74; P < 0.00001). Conclusions: FOLFIRINOX improves OS and offers marginal PFS benefits over gemcitabine but at the cost of increased severe neutropenia. Its use should be considered for patients with good performance status, while further RCTs are necessary to refine patient selection and minimize toxicity. OS in patients on FOLFIRINOX and gemcitabine. Study OS [Months] with FOLFIRINOX SD [Months] FOLFIRINOX Total OS with Gemcitabine [Months] SD [Months] Gemcitabine Total Mean Difference [95% CI] Williet et al 14 23.21 49 9 10.72 49 5.00 [-2.16, 12.16] Santucci et al 12.3 1.59 73 11.3 3.56 73 1.00 [-0.49, 1.51] Riedl et al 10.1 3.27 158 10.1 4.48 297 0.00 [-0.72, 0.72] Rapposelli et al 11.1 10 171 9 9.48 268 0.00 [-1.88, 1.88] Papneja et al 9 9.45 86 9 14.08 86 0.00 [-5.20, 5.20] Ozaka et al 23 20.08 62 21.3 11.95 63 1.70 [-4.10, 7.50] Otsuka et al 11.5 1.62 102 11.1 1.99 153 0.40 [-0.05, 0.85] Muranaka et al 9.9 8.16 16 0 0 22 Not estimable Klein-Brill et al 9.37 1.04 566 6.84 1.19 536 2.53 [2.40, 2.66] Kim et al 13.8 2.72 317 8 2.81 337 1.70 [1.28, 2.12] Hegewisch-Becker et al 11.3 8.59 284 10.7 10.72 489 2.20 [0.82, 3.58] Gourgou-Bourgade et al 11.1 2.3 171 6.8 2.3 171 4.30 [3.81, 4.79] Cui et al 10 7.96 11 9 9.07 79 1.00 [-4.11, 6.11] Conroy et al 11.1 13.68 171 6.8 7 171 4.30 [2.00, 6.60] Chun et al 11.8 1.19 151 10.3 1.19 181 1.50 [1.23, 1.77] Chan et al 9.6 0.963 632 6.1 0.856 498 3.50 [3.39, 3.61] Total (95% CI) 3020 3693 2.82 (2.74, 2.89)