TACE, lenvatinib, and PD-1 inhibitors in unresectable advanced hepatocellular carcinoma: an exploratory retrospective cohort study

For patients with unresectable advanced hepatocellular carcinoma (HCC), therapeutic options are limited, and transarterial chemoembolization (TACE) alone often yields suboptimal outcomes. This study aimed to evaluate clinical outcomes and recorded safety events associated with combining TACE, lenvatinib, and programmed cell death protein 1 (PD-1) inhibitors for HCC. A retrospective cohort study was conducted involving 209 patients with unresectable advanced HCC treated from June 2016 to December 2022. Patients were divided into the TACE + len group ( n = 96) and the TACE + len+PD-1 group ( n = 113). Tumor response, recorded adverse events, treatment exposure, OS, and PFS were analyzed. Propensity score-based IPTW was performed using baseline demographic and clinical variables to reduce measured baseline imbalance. After IPTW adjustment, baseline covariates achieved acceptable balance. Median OS was 16.49 months in the TACE + len+PD-1 group and 13.37 months in the TACE + len group; IPTW-weighted Cox regression showed an association between triple therapy and longer OS (HR = 0.591, 95% CI 0.417–0.836, P = 0.003). Median PFS was 10.02 months and 3.42 months, respectively, and the IPTW-weighted HR for PFS was 0.638 (95% CI 0.479–0.848, P = 0.002). Grade ≥ 3 adverse events occurred in 18.58% and 14.58% of patients, respectively ( P = 0.440). In this exploratory retrospective cohort, adding PD-1 inhibitors to TACE plus lenvatinib was associated with improved tumor response and longer OS/PFS after IPTW adjustment, without a significant increase in recorded Grade ≥ 3 adverse events. These findings require prospective validation.