Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and advanced-stage disease presents significant therapeutic challenges. Combining transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has emerged as a promising strategy to enhance treatment efficacy. This meta-analysis evaluates efficacy and safety of TACE + TKIs + ICIs compared to TKIs + ICIs alone in patients with HCC. METHODS: A systematic search was conducted across "PubMed", "Web of Science", "Cochrane Library", "Scopus", "Google Scholar", and "Embase" to screen studies up to November 2024. Studies comparing TACE + TKIs + ICIs with TKIs + ICIs alone in advanced HCC were included. Outcomes of interest included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events. Results were reported as relative risk (RR) or hazard ratios (HR) with 95% confidence intervals (CI). Funnel plots was used to assess publication bias. RESULTS: Ten studies comprising 1999 patients were included. The combination of TACE + TKIs + ICIs marked improved ORR (RR = 1.81, 95%CI:1.57-2.09, P < 0.00001) and DCR (RR = 1.32, 95%CI: 1.19-1.46, P < 0.00001) comparing with TKIs + ICIs alone. OS and PFS were also significantly prolonged in combination group, with HR of 0.55 (95%CI:0.48-0.63, P < 0.00001) and 0.73 (95%CI:0.65-0.82, P < 0.00001), respectively. Adverse events such as pain (RR = 3.94, 95%CI:2.40-6.47, P < 0.001) and nausea/vomiting (RR = 2.28, 95% CI:1.56-3.33, P < 0.001) were more frequent in the TACE + TKIs + ICIs group, though rates of hypertension, diarrhea, and rash were similar between groups. Funnel plots indicated minimal publication bias for primary outcomes. CONCLUSIONS: The combination of TACE, TKIs, and ICIs significantly improves ORR, DCR, OS, and PFS compared to TKIs and ICIs alone, demonstrating superior efficacy with an acceptable safety profile. These findings provide evidence for the integration of TACE with systemic therapies in the management of HCC.