Transarterial chemoembolization (TACE) with or without immune checkpoint inhibitors in unresectable hepatocellular...

Transarterial chemoembolization (TACE) is the standard of care for intermediate-stage unresectable hepatocellular carcinoma (HCC), but progression-free survival (PFS) with TACE alone remains limited. Recent randomized clinical trials have evaluated the addition of immune checkpoint inhibitors (ICIs) to TACE. We conducted a meta-analysis of randomized trials to assess the efficacy and safety of TACE plus ICIs versus TACE alone in unresectable HCC.

A systematic search of PubMed, Embase, Cochrane Library, and American Society of Clinical Oncology and European Society for Medical Oncology databases was carried out through 15 December 2025 and last updated on 3 June 2026 to identify randomized clinical trials comparing TACE with or without ICIs in unresectable HCC. Outcomes included PFS, objective response rate (ORR), overall survival (OS), and safety. Random-effects meta-analyses were conducted using R software (version 4.5.2, R Foundation for Statistical Computing, Vienna, Austria).

Six randomized clinical trials (EMERALD-1, EMERALD-3, Jia et al., LEAP-012, TALENTACE, and CARES-005) involving 2439 patients were included. Compared with TACE alone, combination therapy improved PFS [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.52-0.77, P < 0.01] and ORR (risk ratio 1.45, 95% CI 1.31-1.61, P < 0.001). OS benefit was borderline (HR 0.85, 95% CI 0.73-0.99, P = 0.04), although data remain immature. Combination therapy was associated with higher rates of any-grade and grade ≥3 adverse events, serious adverse events, and treatment discontinuations.

Adding ICIs to TACE improved PFS and response rates compared with TACE alone in unresectable HCC, at the cost of increased toxicity. OS benefit was borderline and should be interpreted with caution; longer follow-up is required.