TACE and tyrosine kinase inhibitors with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC: a multicenter real-world cohort study

Background and aims This study aimed to evaluate the efficacy and safety of combining transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs), with or without programmed death-1 (PD-1) inhibitors (ICI), as first-line therapy for intermediate-advanced hepatocellular carcinoma (HCC) in a real-world setting. Methods This multicentre retrospective cohort study enrolled patients with intermediate-advanced HCC who received either TACE combined with TKIs and PD-1 inhibitors (TACE-TKI-ICI) or TACE plus TKIs (TACE-TKI) from January 2019 to December 2023. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Propensity score matching (PSM) was used to reduce bias. Results A total of 514 patients with intermediate-advanced HCC were analyzed, 263 patients in the TACE-TKI-ICI group and 251 patients in the TACE-TKI group. After PSM (1:1), 241 patients were included in each group. The TACE-TKI-ICI group had significantly longer median PFS (13.8 vs. 10.8 months; hazard ratio [HR] = 0.73; 95% confidence interval [CI], 0.58–0.91; p = 0.005) and OS (22.6 vs. 16.7 months; HR = 0.71; 95% CI, 0.55–0.91; p = 0.006) than the TACE-TKI group. The ORR was also better (58.9% vs. 41.5%, p < 0.001) in the TACE-TKI-ICI group. The incidence of grade 3/4 adverse events was 10.8% in the TACE-TKI-ICI group and 8.3% in the TACE-TKI group. Conclusion Adding PD-1 inhibitors to TACE and TKIs as first-line therapy for intermediate-advanced HCC can improve PFS, OS, and ORR, while being well tolerated.