Abstract
BACKGROUND: More than 60% of patients with hepatocellular carcinoma (HCC) are diagnosed at the intermediate-advanced stages, which are not amenable to surgical resection and ablation. The optimal treatment plan for patients with unresectable HCC remains controversial. This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKI) plus programmed death receptor-1 (PD-1) inhibitors (TACE + TKI + PD-1) versus TACE combined with TKI (TACE + TKI) among patients with unresectable HCC. METHODS: A comprehensive search of the PubMed, EMBASE and the Cochrane Library databases was performed, and all studies related to TACE + TKI + PD-1 and TACE + TKI for treatment of HCC were included. We calculated risk ratio (RR) and mean difference for dichotomous and continuous outcomes. Data were analyzed using RevMan5.4 and Stata 17.0. We conducted a subgroup analysis based on specific types of TKI. RESULTS: A total of 12 retrospective studies were included in the analysis, involving 1,078 patients in the TACE + TKI + PD-1 group and 1,332 in the TACE + TKI group. Compared with the TACE + TKI group, the TACE + TKI + PD-1 group showed prolonged overall survival [RR =7.39, 95% confidence interval (CI): 5.69-9.08, P<0.001, I(2)=90%], progression-free survival (RR =3.89, 95% CI: 3.21-4.57, P<0.001, I(2)=81%)and higher objective response rate (RR =1.38, 95% CI: 1.26-1.51, P<0.001, I(2)=49%). Similarly, the 1-year survival rate improved (RR =5.92, 95% CI: 4.43-5.92, P<0.001, I(2)=11%) in the TACE + TKI + PD-1 group. No significant difference was found in adverse events between the two groups. CONCLUSIONS: TACE + TKI + PD-1 significantly improved survival outcomes and demonstrated superior efficacy and a manageable safety profile in the systemic treatment of patients with unresectable HCC.