Network Meta-analysis of First-Line Systemic Treatment for Patients With Metastatic Colorectal Cancer

Abstract

Purpose To assess the relative efficacy and safety of first-line systemic therapies in patients with metastatic colorectal cancer. 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 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 Grade 3 + adverse events (AEs). 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 for OS and PFS. Results A total of 30 RCTs comprising 12,146 mCRC patients with 25 different treatment 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 well-tolerated 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.

Comparison of the Effectiveness of Radiotherapy with 3D-CRT, IMRT, VMAT and PT for Newly Diagnosed Glioblastoma: A Bayesian Network Meta-Analysis

“…As all analyses were performed on data from previously published trials, it was not necessary to obtain ethical approval or patient consent. The methodology for the Bayesian network meta-analysis followed the established procedures described previously [16,17]. In this work, we conducted a comprehensive synthesis of evidence focusing on two primary outcomes: progression-free survival (PFS) and overall survival (OS).…”

Selective vulnerability of ARID1A deficient colon cancer cells to combined radiation and ATR-inhibitor therapy

“…Colorectal cancer (CRC), one of the most frequently occurring cancers, is still one of the main causes of cancerassociated mortality globally (1). Typically, CRC results from successively acquired genetic and epigenetic alterations, mainly related to proto-oncogene activation and loss of tumor suppressor function (2,3). Standard treatments have failed so far to significantly improve the survival of CRC patients, and as a result novel, targeted and more selective therapy options are urgently needed.…”