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 I2 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.