Efficacy and safety of local treatments combined with targeted therapy and immunotherapy versus targeted therapy plus immunotherapy alone in hepatocellular carcinoma: A meta-analysis

BACKGROUND: Beyond surgical intervention, hepatocellular carcinoma is mainly treated with 3 main approaches: transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) as local treatment, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs). Up to now, clinical experts have not reached a consistent consensus on how to reasonably select combination therapy. Therefore, we performed this research to contrast the clinical outcomes of local treatment plus ICIs and TKIs (Local-ICIs-TKIs) with ICIs and TKIs, aiming to offer a practical reference basis for clinical practice. METHODS: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases on the computer, covering literature from their establishment to August 1st, 2025, for (Local-ICIs-TKIs) compared to ICIs and TKIs Clinical Investigation. The primary outcome indicators were treatment-related adverse events, median overall survival, median progression-free survival, objective response rate, and disease control rate. All statistical analyses were conducted using Stata 17 statistical software in this study. RESULTS: We screened 15 relevant pieces of literature, including 3208 patients. Compared with the ICIs-TKIs group, the Local-ICIs-TKIs treatment enhanced the pooled disease control rate (relative risk = 1.27; 95% confidence interval [CI]: 1.21-1.33) and objective response rate (relative risk = 1.87; 95% CI: 1.71-2.05). The combination therapy individually prolonged the median progression-free survival (hazard ratio = 0.59; 95% CI: 0.47-0.71) and median overall survival (hazard ratio = 0.48; 95% CI: 0.40-0.56). TACE and HAIC significantly elevated the risks of abdominal pain, anorexia, nausea, appetite loss, leukopenia, and liver injury. HAIC exhibited a higher incidence of abdominal pain, whereas TACE was more likely to lead to severe liver injury. The majority of adverse events were mild to moderate, and both interventions demonstrated favorable safety. CONCLUSION: In comparison to the foundation of ICIs-TKIs systemic therapy, the addition of TACE or HAIC treatment exhibits good tolerability and can further yield superior clinical responses and prolong survival time for hepatocellular carcinoma patients.