Transarterial chemoembolization combined with lenvatinib transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: A systematic review and meta-analysis.

Background: Lenvatinib and sorafenib are tyrosine kinase inhibitors that are effective in the treatment of unresectable hepatocellular carcinoma (uHCC). The efficacy of which of them is better suited to combine transarterial chemoembolization (TACE) for the treatment of uHCC is ripe.

Aim: To compare the effectiveness of TACE combined with lenvatinib (TACE-lenvatinib) and TACE combined with sorafenib (TACE-sorafenib) in the treatment of uHCC, this study was carried out.

Methods: Publicly available studies comparing the efficacy of TACE-lenvatinib and TACE-sorafenib in the treatment of uHCC were collected from PubMed, Embase and Cochrane Library, with a cut-off date of December 2024. Stata SE 15 software was used for statistical analysis.

Results: A total of six studies involving 547 patients were included, 248 in the TACE-lenvatinib group and 299 in the TACE-sorafenib group. Meta-analysis results showed that TACE-lenvatinib was more effective than TACE-sorafenib in complete response [relative risk (RR) = 1.81, 95% confidence interval (CI): 1.11-2.96, = 0.02], partial response (RR = 1.38, 95%CI: 1.12-1.70, = 0.002), objective response rate (RR = 1.47, 95%CI: 1.24-1.74, < 0.0001) and disease control rate (RR = 1.22, 95%CI: 1.00-1.49, = 0.05). TACE-lenvatinib was significantly lower than TACE-sorafenib in progressive disease rate (RR = 0.54, 95%CI: 0.39-0.74, = 0.002). No significant difference was found in stable disease rate (RR = 0.89, 95%CI: 0.60-1.33, = 0.58) between the two groups. TACE-lenvatinib was significantly more effective than TACE-sorafenib in overall survival (hazard ratio = 2.00, 95%CI: 1.59-2.50, < 0.05) and progression free survival (hazard ratio = 2.04, 95%CI: 1.49-2.86, < 0.05). As regards adverse events, TACE-lenvatinib was better in reducing the incidence of hypertension than TACE-sorafenib, while no significant difference was found in overall adverse events, abdominal pain, fever, fatigue, nausea and vomiting, decreased appetite, liver dysfunction, hand-foot skin reaction, diarrhea, thrombocytopenia, and rash between the two groups.

Conclusion: In patients with uHCC, TACE-lenvatinib induced a better tumor response rate and survival outcome than TACE-sorafenib, while TACE-lenvatinib resulted in a higher incidence of hypertension than TACE-sorafenib. However, these conclusions are derived from currently available medical evidence, and further confirmation by more rigorously designed randomized controlled studies is still needed.