OBJECTIVES: FOLFIRINOX, Gemcitabine Nab-paclitaxel (gem-nab/P), and Gemcitabine Capecitabine (gem-cap) have demonstrated superiority over gemcitabine monotherapy and are the standard treatments for resectable and advanced pancreatic cancer (PC). It is still unclear which chemotherapy regimen is the most optimal. Therefore, this study aimed to conduct a systematic review and meta-analysis to compare safety and efficacy of FOLFIRINOX vs. gem-nab/P and gem-cap in resectable and advanced PC.

METHODS: A systematic review was conducted in multiple databases including PubMed, Embase, Cochrane Central Registry of Controlled Trials, and clinicaltrials.gov from inception to September 2020. Phase III randomized controlled trials investigating resectable or advanced PC patients treated with FOLFIRINOX, gem-nab/P, or gem-cap were included. Primary outcomes including overall survival (OS), disease free survival (DFS)/progression free survival (PFS)/relapse free survival (RFS), grade 3/4 adverse events (AE) were pooled using a random-effects model. Indirect comparisons were done to compare FOLFIRINOX vs. gem-cap and gem-nab/P. Heterogeneity was evaluated using Cochran’s Q test and I² statistics. Risk of bias was assessed using Cochrane Risk of Bias Tool for Randomized Trials. Publication bias was measured using Egger’s test.

RESULTS: Nine studies were identified involving 6,564 patients. Indirect comparisons showed FOLFIRINOX had significantly better OS (resectable: HR 0.78, 95% CI 0.61-0.99, advanced: HR 0.71, 95% CI 0.60-0.85) and RFS/DFS/PFS (resectable: HR 0.67, 95% CI 0.55-0.82, advanced: HR 0.65, 95% CI 0.57-0.74) compared to gem-cap. FOLFIRINOX also showed significantly better OS (resectable: HR 0.78, 95% CI 0.61-1.00, advanced: HR 0.73, 95% CI 0.54-0.98) and DFS/PFS (resectable: HR 0.66, 95% CI 0.53-0.82, advanced: HR 0.64, 95% CI 0.49-0.83) compared to gem-nab/P. FOLFIRINOX increased drug-related risk of grade 3/4 AEs compared to gem-cap and gem-nab/P.

CONCLUSIONS: This study suggests that FOLFIRINOX is associated with significant survival benefits compared to gem-nab/P and gem-cap. However, it is important to consider the increased risk for grade 3/4 AEs associated with FOLFIRINOX.