Relative Efficacy of Systemic Treatments for Patients with Advanced Hepatocellular Carcinoma According to Viral Status: A Systematic Review and Network Meta-Analysis

Background Several clinical trials that tested the efficacy of systemic treatments for advanced hepatocellular carcinoma (HCC) showed a tendency that patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection had different survival benefits from targeted agents. Objective The objective of this study was to assess the comparative efficacy of systemic targeted therapies according to HBV and HCV status in first-line and second- or later-line treatments for advanced HCC. Methods PubMed, EMBASE, Cochrane database, and meeting abstracts were searched through to January 2019. A Bayesian network meta-analysis was performed to estimate hazard ratios (HRs) for overall survival with 95% credible intervals (CrIs) and determine the ranking of the included regimens. Results Sixteen trials involving 6410 patients were included in the meta-analysis. In the first-line treatment setting, lenvatinib was the best agent for both HBV and HCV subgroups, presenting the most favorable HR versus sorafenib (HR 0.83, 95% CrI 0.68–1.01 and HR 0.91, 95% CrI 0.66–1.25, respectively), and was ranked as the best agent [surface under the cumulative ranking curve (SUCRA) value of 87% and 85%, respectively] among the included drugs. In second-line therapy, regorafenib showed the lowest HR versus placebo (HR 0.58, 95% CrI 0.41–0.82) in the HBV subgroup, whereas no agent was significantly more effective than placebo in the HCV subgroup. Conclusions Compared with sorafenib, lenvatinib was more efficacious in the HBV subgroup than in the HCV subgroup, and the relative ranking of sorafenib in the HBV subgroup was lower than in the HCV subgroup. Each targeted agent reported to be the best by viral etiology and line of treatment could be carefully recommended in each subgroup.