Systematic Review and Meta-Analysis of Multitargeted Tyrosine Kinase Inhibitors in Patients With Intractable Metastatic Colorectal Cancer

Abstract

Background: The treatment options for intractable metastatic colorectal cancer include regorafenib, trifluridine/tipiracil, and fruquintinib. In this study, we aimed to conduct a network meta-analysis for comparing the efficacy of these agents. Methods: We searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials databases for relevant literature, up to February 2020. The data were collected from randomized controlled trials on regorafenib, trifluridine/tipiracil, or fruquintinib, administered to patients with metastatic colorectal cancer who failed on treatment with oxaliplatin, irinotecan, or fluoropyrimidine. The primary end points, namely, the overall survival and progression-free survival, were analyzed for subsequent network analysis using the Review Manager and Aggregate Data Drug Information System software for performing direct and indirect comparisons. Results: A total of 7 trials were analyzed in this study. Trifluridine/tipiracil and regorafenib proved to be superior to the placebo, with respect to the overall survival (odds ratio: 0.38, 95% confidence interval: 0.27-0.52 for trifluridine/tipiracil; odds ratio: 0.47, 95% confidence interval: 0.26-0.84 for regorafenib) and progression-free survival (odds ratio: 0.18, 95% confidence interval: 0.05-0.67 for trifluridine/tipiracil; odds ratio: 0.06, 95% confidence interval: 0.04-0.09 for regorafenib). Regorafenib (80 mg) was superior to the placebo in terms of the overall survival and progression-free survival and inferior to trifluridine/tipiracil and fruquintinib. Network analysis revealed that the efficacy of trifluridine/tipiracil and fruquintinib was fundamentally similar, and both the agents were superior to regorafenib. Conclusion: Regorafenib (80 mg) was superior to the placebo, but inferior to 160 mg regorafenib, trifluridine/tipiracil, and fruquintinib. This study further revealed that the efficiency of trifluridine/tipiracil and fruquintinib is identical, but their toxicity profiles are different.