TACE-HAIC plus TKIs with/without PD-1 inhibitors for unresectable hepatocellular carcinoma: a propensity score matching study.

BACKGROUND AND AIMS: Patients with unresectable hepatocellular carcinoma (uHCC) have a poor prognosis, and effective systemic treatment options remain limited. We aimed to evaluate the safety and efficacy of adding programmed death-1 (PD-1) inhibitors to transarterial chemoembolization combined with hepatic arterial infusion chemotherapy (TACE-HAIC)+lenvatinib. METHODS: We retrospectively analyzed data from patients with uHCC who received TACE-HAIC+lenvatinib, without or with PD-1 inhibitors (n = 124). Patients were stratified into a triple-therapy group (TACE-HAIC+lenvatinib; n = 71) and a quadruple-therapy group (TACE-HAIC+lenvatinib+PD-1 inhibitors; n = 53), based on whether PD-1 inhibitors were included in the first-line regimen. Overall survival (OS), progression-free survival (PFS), and adverse event rate were compared between the groups. Propensity score matching was performed to reduce confounding bias. RESULTS: After propensity score matching (PSM), 43 matched pairs were identified. The median OS was 11.0 months [95% confidence interval (CI), 10.0-16.0] in the triple-therapy group and 25.0 months (95% CI: 12.0-not reached) in the quadruple-therapy group. The median PFS was 8.6 months (95% CI: 6.37-11.77) and 12.1 months (95% CI: 8.7-not reached), respectively. Both OS and PFS were significantly improved in the quadruple-therapy group (P < 0.05). CONCLUSIONS: The addition of PD-1 inhibitors to TACE-HAIC plus lenvatinib significantly improved both OS and PFS without a statistically significant increase in adverse events. However, careful monitoring and prompt management of immune-related adverse events remain warranted during treatment.