Hepatocellular carcinoma (HCC) often presents as unresectable, necessitating effective treatment modalities. Combining transarterial chemoembolization (TACE) with immunotherapy and targeted therapy has shown promise, yet real-world evidence is needed. To investigate effectiveness and safety of TACE with tislelizumab ± targeted therapy for unresectable HCC in real-world setting. This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab. The clinical outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). All patients were evaluated according to the mRECIST criteria. The adverse event (AE) was also assessed. In this study of 56 patients with median follow-up of 10.9 months, 7 had previous immunotherapy. Tislelizumab was administered before TACE in 21 (37.50%) and after in 35 (62.50%) patients, with 91.07% receiving concurrent targeted therapy. Median PFS was 14.0 (95%CI: 7.0-18.00) months, and OS was 28 (95%CI: 2.94-53.05) months. Patients with prior immunotherapy had shorter PFS (6 vs. 18 months, P = 0.006). Overall ORR and DCR were 82.14% and 87.50%. Grade ≥ 3 treatment-related AEs included increased alanine aminotransferase (8.93%), aspartate aminotransferase (10.71%), and total bilirubin (3.57%). The combination of TACE and tislelizumab, with or without targeted therapy, demonstrated promising efficacy and safety in unresectable HCC, especially in immunotherapy-naive patients, warranting further prospective validation studies.
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