Abstract
BACKGROUND: Transarterial chemoembolization (TACE) is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC); however, its survival benefits remain unsatisfactory. In this systematic review, we aimed to compare the clinical outcomes of tyrosine kinase inhibitors (TKIs) combined with TACE and TACE alone in patients with intermediate-stage HCC. METHODS: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Randomized controlled trials (RCTs) comparing TACE plus TKIs with TACE alone in patients with HCC were retrieved from PubMed, Embase, and the Cochrane Library. The primary outcomes included overall survival (OS) and progression-free survival (PFS), reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes included the overall response rate (ORR) and disease control rate (DCR), which were analyzed using risk ratios (RRs). Heterogeneity was assessed using the I(2) statistic. RESULTS: Fourteen RCTs were included in this meta-analysis. Compared to TACE alone, TACE plus TKIs significantly improved PFS (HR = 0.74, 95% CI: 0.59-0.93, p = 0.01, I(2) = 87%) and the ORR (RR = 1.29, 95% CI: 1.11-1.51, p = 0.001), but not OS (HR = 0.84, 95% CI: 0.69-1.03, p = 0.10, I(2) = 65%) and the DCR (RR = 1.05, 95% CI: 0.99-1.11, p = 0.08). Subgroup analysis showed that TACE plus TKIs significantly increased OS in patients with hepatitis B virus (HBV) infection (HR = 0.67, 95% CI: 0.51-0.88), but not in those with hepatitis C virus (HCV) infection or those without HBV and HCV infection. Moreover, patients with HBV infection, male patients, and those with a good functional status (ECOG performance status of 0) had better PFS than others. CONCLUSIONS: Compared with TACE alone, TACE combined with TKIs can significantly improve PFS and the ORR in patients with intermediate-stage HCC. Furthermore, combination treatment can significantly improve OS in patients with HBV infection, but not in patients with HCV infection. Further research is required to optimize patient selection and treatment strategies.