Comparative safety and efficacy of hepatic arterial infusion chemotherapy combined with targeted therapy and immunotherapy, with or without transarterial chemoembolization, in unresectable hepatocellular carcinoma: a multicenter retrospective cohort

BACKGROUND: Interventional therapies and systemic chemotherapy are the mainstay of treatment for patients with unresectable hepatocellular carcinoma (HCC). This study aimed to generate preliminary evidence regarding the feasibility and safety of transarterial chemoembolization (TACE) combined with hepatic artery infusion chemotherapy (HAIC), targeted therapy, and immunotherapy in patients with unresectable hepatocellular carcinoma (HCC). METHODS: This retrospective study analyzed 213 patients with unresectable HCC treated with TACE plus HAIC, targeted therapy, and immunotherapy (THTI) or HAIC plus targeted therapy and immunotherapy (HTI) between July 2019 and August 2023. Propensity score matching (PSM) was used to balance potential confounders between patients in the THTI and HTI groups. Overall survival (OS) was assessed using Kaplan-Meier analysis, and the log-rank test was used for between-group comparisons. Cox proportional hazards regression models were used to identify independent influences on patient OS. RESULTS: A total of 213 patients were treated with THTI (n = 41) or HTI (n = 172). After 1:2 PSM, there were 31 patients in the THTI and 62 patients in the HTI groups. After PSM, OS was significantly better in the THTI than in the HTI groups (34.4 vs. 16.3 months, P = 0.013). The objective response rate (ORR) (38.71% vs. 45.16%, P = 0.554) and disease control rate (DCR) (80.65% vs. 79.03%, P = 0.856) were not statistically significant in the THTI and HTI groups. THTI treatment is an independent predictor of OS. All adverse events (AEs) in the THTI and HTI groups were manageable. CONCLUSION: Compared with HTI, THTI was associated with improved OS in patients with unresectable HCC, with manageable short-term AEs. Quadruple therapy showed encouraging antitumor activity in this retrospective cohort and should be considered exploratory, further large-scale prospective studies are required.