Hepatic arterial infusion chemotherapy combined with donafenib and tislelizumab versus transcatheter chemoembolization alone for hepatocellular carcinoma: A propensity score matching study.

4094 Background: Although tyrosine kinase inhibitors combined with PD-1/L1 inhibitors have been established as first-line treatment for advanced hepatocellular carcinoma (HCC), the survival benefit remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) has emerged as an effective therapy to improve the prognosis of HCC patients. This study aimed to investigate the efficacy and safety of HAIC combined with donafenib and tislelizumab in HCC. Methods: 421 patients diagnosed as HCC and treated in Sun Yat-sen University Cancer Center from January 2017 to December 2024 were enrolled in this retrospective study, included 151 patients received FOLFOX-HAIC combined with donafenib and tislelizumab (DT-HAIC) and 270 received transcatheter chemoembolization (TACE) alone. To avoid the selection bias and balance covariates, we conducted propensity score matching (PSM). The primary outcomes are progression-free survival (PFS) and overall survival (OS); the secondary outcomes include objective response rate (ORR), disease control rate (DCR) and safety. Tumor response was evaluated per RECIST v1.1. Results: PSM resulted in 151 matched pairs with comparable baseline characteristics between the DT-HAIC and TACE cohorts. Compared with the TACE cohort, Patients receiving DT-HAIC exhibited significantly better median PFS (10.3 vs 4.9 months, P < 0.01) and median OS (not reached vs 10.9 months, P < 0.01). The ORR and DCR were significantly higher in the DT-HAIC cohort than in the TACE cohort (ORR: 33.8% vs 11.3%, P < 0.01; DCR: 77.9% vs 65.3%, P = 0.03). There was no treatment-related death. Serious adverse events were similar between the two groups, except for alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelet count, abdominal pain and allergic reaction. In the TACE cohort, the occurrence of Grade 3-4 elevations in ALT (11.3% vs 21.9%, P = 0.02) and AST (21.2% vs 36.4%, P < 0.01), as well as abdominal pain (2.6% vs 16.6%, P < 0.01), was more prevalent. In contrast, the DT-HAIC cohort exhibited a higher incidence of Grade 3-4 thrombocytopenia (11.3% vs 1.3%, P < 0.01) and allergic reactions (4.6% vs 0, P = 0.02). Conclusions: DT-HAIC significantly improved PFS, OS, ORR, and DCR compared with TACE alone, with manageable adverse events, suggesting that the combination of HAIC with donafenib and tislelizumab may be a promising treatment option for HCC patients. DT-HAIC (n=151) TACE (n=151) P Value mPFS 10.3m 4.9m P<0.01 mOS Not reached 10.9m P<0.01 ORR 33.8% 11.3% P<0.01 DCR 77.9% 65.3% P=0.03