AUTHOR=Wang Fengliang , Cao Zhenxue , Yu Chunpeng , Li Jian , Li Qun , Chang Shuai , Zhang Shuo , Wang Song 

TITLE=Tislelizumab plus tyrosine kinase inhibitors with TACE improves survival in unresectable hepatocellular carcinoma with clinical predictors and manageable safety

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1664519

DOI=10.3389/fimmu.2025.1664519

ISSN=1664-3224

ABSTRACT=Background & AimsThe survival benefit of adding transarterial chemoembolization (TACE) to systemic therapy (tislelizumab plus tyrosine kinase inhibitors [TKIs]) for unresectable hepatocellular carcinoma (HCC) requires validation. This retrospective study compared the efficacy and safety of tislelizumab-TKIs with or without TACE and identified clinical predictors of benefit.MethodsThis retrospective analysis included 283 unresectable HCC patients: systemic therapy alone (STG, n=98; tislelizumab plus TKIs) versus combination therapy (CTG, n=185; tislelizumab plus TKIs and TACE). Primary endpoints were overall survival (OS) and progression-free survival (PFS), analyzed by Cox regression. Propensity score matching (PSM) was used to reduce baseline differences between the two groups.ResultsAfter PSM, CTG significantly improved median OS (22.5 [95% confidence interval (CI): 19.0–34.4] vs. 14.0 [12.1–18.6] months; hazard ratio (HR) 0.53, p<0.001) and PFS (14.6 [12.1–19.1] vs. 9.5 [7.8–12.5] months; HR 0.59, p<0.001) versus STG. Multivariate analysis identified independent predictors of poor OS: age <60 years, extrahepatic spread, portal vein thrombus, alpha-fetoprotein (AFP) ≥400 ng/mL, and elevated gamma-glutamyl transferase (GGT). Subgroups with maximal CTG benefit included patients aged ≥60 years, no extrahepatic spread, AFP <400 ng/mL, and normal GGT. CTG had higher all-grade adverse events (79.6% vs. 67.0%, p=0.021) and grade ≥3 events (23.5% vs. 14.1%, p=0.038), primarily manageable liver toxicity and hematological abnormalities.ConclusionCombining TACE with tislelizumab-TKIs significantly improves survival over systemic therapy alone in unresectable HCC, with maximal benefit observed in patients aged ≥60 years, without extrahepatic spread, with AFP <400 ng/mL, or normal GGT, despite increased manageable toxicity.