Transarterial chemoembolization combined with immune checkpoint inhibitors and anti-VEGF agents for intermediate HCC: a multicenter study.

PURPOSE: To compare the clinical outcomes and safety profiles of immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor (VEGF) agents alone versus transarterial chemoembolization (TACE) combined with ICI and anti-VEGF agents in patients with intermediate hepatocellular carcinoma (HCC).

METHODS: Patients were stratified into two groups: the triple-therapy (TACE combined with ICI and anti-VEGF agents) and dual-therapy groups (ICI plus anti-VEGF agents). Stabilized inverse probability of treatment weighting (sIPTW) was applied to balance baseline characteristics. Study endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors. Safety was evaluated per CTCAE v5.0.

RESULTS: After sIPTW adjustment, the triple-therapy group demonstrated significantly longer median PFS (20.0 vs. 14.0 months; P < 0.0001) and median OS (26.0 vs. 19.0 months; P < 0.0001) compared to the dual-therapy group. Tumor response was also superior in the triple-therapy group, with higher ORR (63.3 % vs. 39.4 %; P = 0.015) and DCR (85.0 % vs. 60.6 %; P < 0.001). IPTW-weighted Cox regression identified AFP, tumor response, and up-to-7 criteria as independent prognostic factors for PFS, while AFP, up-to-7 criteria, and cirrhosis were independent factors for OS. The safety profile was manageable in both groups, with no new safety signals identified.

CONCLUSION: This study demonstrates that combining TACE with ICIs and anti-VEGF agents significantly improves PFS, OS, ORR and DCR in intermediate-stage HCC patients compared to dual ICI and anti-VEGF agents therapy, with manageable toxicity.