Abstract
PURPOSE: This study was designed to compare the safety and efficacy of transarterial chemoembolization (TACE) plus hepatic arterial infusion chemotherapy (HAIC) or TACE combined with lenvatinib (LEN) and PD-1 inhibitors (PD-1i) in large intermediate-stage hepatocellular carcinoma (iHCC). METHODS: This multi-center retrospective study was conducted at four tertiary medical centers. From January 01, 2021, to June 30, 2024, 221 patients with large iHCC undergoing TACE-HAIC-LEN-PD-1i (THLP group, n=103) or TACE-LEN-PD-1i (TLP group, n=118) were enrolled. Local tumor responses, survival, and treatment-related adverse events (TRAEs) were analyzed between the THLP and TLP groups. RESULTS: Baseline characteristics were well-balanced between the two groups (P>0.05). Objective response rate (70.8% vs. 44.9%, P<0.001) and disease control rate (91.2% vs. 78.8%, P=0.011) in the THLP group were significantly superior over those in the TLP group. Compared to the TLP group, the THLP group achieved significantly better median progression-free survival (11.0 vs. 8.0 months, P<0.001) and median overall survival (29.9 vs. 20.3 months, P<0.001). The incidence of conversion to resection was obviously higher in the THLP group than that in the TLP group (20.4% vs.9.3%, P=0.020). The frequency of any grade or grade 3-4 TRAEs was comparable between the two groups, associating with no statistical differences (P>0.05). No grade 5 TRAEs and treatment-related mortality were observed. CONCLUSION: TACE-HAIC-LEN-PD-1i was safe and well-tolerated, and achieved better efficacy than TACE-LEN-PD-1i in patients with large iHCC. Further randomized controlled trials are required to validate the benefits of TACE-HAIC-LEN-PD-1i.