Comparative Safety and Efficacy of Therapeutic Options in Resectable and Advanced/Metastatic Pancreatic Cancer: A Systematic Review and Indirect Comparison

Objectives: FOLFIRINOX, gemcitabine/nab-paclitaxel (gem-nab/P), and gemcitabine-capecitabine (gem-cap) demonstrated superiority over gemcitabine monotherapy for pancreatic cancer (PC). It is still unclear which chemotherapy regimen is the most optimal. This study aimed to conduct a systematic review (SR) and indirect comparison to compare safety and efficacy of FOLFIRINOX versus gem-nab/P and gem-cap in PC. Methods: An SR was conducted in several databases from inception to November 2020. RCTs investigating resectable or advanced PC were included. Primary outcomes including overall survival (OS), disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS), and grade 3/4 adverse events (AEs) were pooled using a random effects model. Indirect comparisons were done to compare FOLFIRINOX versus gem-cap and gem-nab/P. Heterogeneity was evaluated using Cochran's Q test and I-2 statistics. Results: Nine studies were identified involving 6,564 patients. Indirect comparisons showed FOLFIRINOX had significantly better OS (resectable: HR 0.78 [0.61-0.99]; advanced: HR 0.71 [0.60-0.85]) and RFS/DFS/PFS (resectable: HR 0.67 [0.55-0.82]; advanced: HR 0.65 [0.57-0.74]) compared to gem-cap as well as OS (resectable: HR 0.78 [0.61-1.00]; advanced: HR 0.73 [0.54-0.98]) and DFS/PFS (resectable: HR 0.66 [0.53-0.82]; advanced: HR 0.64 [0.49-0.83]) compared to gem-nab/P. FOLFIRINOX increased grade 3/4 AE risk compared to gem-cap and gem-nab/P. Conclusions: FOLFIRINOX is associated with significant survival benefits compared to gem-nab/P and gem-cap. However, it is important to consider the increased grade 3/4 AE risk associated with FOLFIRINOX.