Stage-Dependent Efficacy of TACE Combined with Tyrosine Kinase and Immune Checkpoint Inhibitors as Conversion Therapy...

This study was designed to compare the efficacy and safety of transarterial chemoembolization (TACE) alone versus TACE combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) as conversion therapy for patients with initially unresectable hepatocellular carcinoma (HCC), and to identify which patient populations benefit most from triple combination therapy.

This multicenter retrospective study included 260 patients with initially unresectable HCC treated at 7 centers in China between January 2020 and January 2025. Of these, 150 received triple conversion therapy (TACE + TKI + ICI) and 110 received TACE alone. Inverse probability of treatment weighting (IPTW) was applied to minimize confounding. Overall survival (OS), progression-free survival (PFS), tumor response, conversion hepatectomy rates, and treatment-related adverse events (TRAEs) were compared between the two groups.

After IPTW, all standardized mean differences were < 0.10. Triple therapy was associated with significantly longer median OS (31.0 vs 16.5 months; HR 0.51, 95% CI: 0.39-0.68, P < 0.001) and PFS (10.2 vs 5.8 months; HR 0.55, 95% CI: 0.43-0.72, P < 0.001), with benefit maintained after IPTW adjustment. The modified RECIST objective response rate (59.3% vs 29.1%) and conversion hepatectomy rate (34.7% vs 12.7%) were both higher with triple therapy (both P < 0.001). The OS benefit was significant in BCLC stage B (HR 0.37, P < 0.001) and stage C (HR 0.47, P < 0.001) but not stage A (HR 0.78, P = 0.480). Grade 3-4 TRAEs did not differ significantly (30.0% vs 24.5%, P = 0.406).

Triple conversion therapy was well tolerated and provided superior efficacy over TACE alone in patients with intermediate- or advanced-stage unresectable HCC. No significant survival difference was detected in early-stage (BCLC stage A) disease, supporting a stage-stratified approach to conversion therapy selection.