Systemic therapy as First-Line Treatment for Patients with Metastatic Colorectal Cancer: A Systematic Review and Network meta-analysis of Randomized Clinical Trials

Purpose: To assess the relative efficacy and safety of first-line systemic therapies in patients with metastatic CRC (mCRC). Experimental Design: A comprehensive literature review was conducted including MEDLINE, Embase, and the Cochrane Central Registry of Controlled Trials for phase II or III Randomized Controlled Trials (RCTs) published up to and including July 15, 2019.We included RCTs in which at least 1 intervention was either a chemotherapeutic agents (such as, fluorouracil, irinotecan, or oxaliplatin) or antibodies targeting angiogenesis (such as, bevacizumab) or agents that act on the epidermal growth factor receptor pathway (such as, cetuximab and panitumumab) or studies reported at least one of the following outcomes: Overall Survival (OS), Progression-Free Survival (PFS) and/or serious adverse events (SAEs). Using a random effect model, we performed a Bayesian network meta-analysis to analyze the probability of optimal therapeutic regime obtained from direct comparisons with indirect evidences. We estimated hazard ratios (HRs) for OS and PFS. Results: : A total of 30 RCTs comprising (12, 146 patients with mCRC comparing 25 different strategies were included. The triple combination FOLFOXIRI [fluorouracil, leucovorin, oxaliplatin, and irinotecan] plus bevacizumab provided significant survival benefits with improved OS over all other treatments. The network meta-analysis also indicated a significant advantage of using FOLFOXIRI plus bevacizumab in comparison to other treatment strategies for PFS. Besides, FOLFOXIRI plus bevacizumab was associated with the lowest risk of serious adverse events. Conclusions: : Our study supported the use of FOLFOXIRI plus bevacizumab as the best first-line regimen and potentially effective and safe strategy for the management of patients with mCRC.