Triple therapy combining transarterial chemoembolisation (TACE), tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICIs) has shown efficacy in unresectable hepatocellular carcinoma (HCC), but evidence in elderly patients and the role of sarcopenia remain unclear. We enrolled 231 patients aged ≥ 65 years with unresectable HCC who received triple therapy (TACE + TKI + ICI; n = 80) or TACE alone (n = 151) across seven centres in China (2019-2023). Sarcopenia was defined by sex-specific L3 skeletal muscle index (SMI) cutoffs (males: 42 cm2/m2; females: 38 cm2/m2). Inverse probability of treatment weighting (IPTW) adjusted for confounding, and treatment-sarcopenia interaction was assessed via weighted Cox regression. After IPTW adjustment, triple therapy significantly improved overall survival (OS; median 12.6 vs 9.3 months; hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.26-2.20; p < 0.001) and progression-free survival (median 6.2 vs 4.2 months; HR 1.86, 95% CI 1.40-2.47; p < 0.001). Sarcopenia was present in 100 patients (43.3%) and significantly modified the treatment effect (p for interaction = 0.049). Among non-sarcopenic patients (n = 131), triple therapy conferred a substantial survival benefit (median OS 19.3 vs 10.6 months; HR 1.97; p < 0.001), whereas no significant benefit was observed in sarcopenic patients (n = 100; median OS 10.4 vs 8.7 months; HR 1.20; p = 0.460). Grade ≥ 3 adverse events were comparable between groups (26.2% vs 16.6%; p = 0.086). These findings support routine sarcopenia assessment to guide treatment selection in elderly patients with unresectable HCC.
Keywords: Elderly; Hepatocellular carcinoma; Immune checkpoint inhibitors; Sarcopenia; Transarterial chemoembolisation; Triple therapy; Tyrosine kinase inhibitors.
© 2026. The Author(s).