Retrospective observational study of transcatheter arterial chemoembolization (TACE) combined with PD-1 inhibitor and tyrosine kinase inhibitor (TKI) in advanced hepatocellular carcinoma.

Abstract

Transcatheter arterial chemoembolization (TACE) induces tumor necrosis and antigen release, but the resulting hypoxic microenvironment upregulates programmed death-ligand 1and vascular endothelial growth factor, providing a biological rationale for adding a programmed death-1 (PD-1) inhibitor and a TKI. The study aims to assess the effectiveness and safety of a treatment regimen consisting of TACE, tyrosine kinase inhibitors, and PD-1 inhibitors in patients diagnosed with advanced hepatocellular carcinoma (HCC) that cannot be treated surgically. This retrospective observational study (Jiangxi Cancer Hospital, Jan 2021-Jun 2023) enrolled 52 advanced HCC patients, with 45 included in final analysis. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints covered objective response rate, Disease Association for the Study of the Liver and safety. Survival was analyzed via Kaplan-Meier method and Cox proportional hazards regression. The cohort comprised 38 men and 7 women with a mean age of 50.9 ± 12.06 years, and 36 patients (80.0%) were hepatitis B virus antigen positive. At 6 months, the PFS rate stood at 71.1%, while at twelve months, it was recorded at 51.7%. The median PFS reached 12.4 months (95% confidence interval: 9.8-15.0), while the median OS was found to be 24.2 months (95% confidence interval: 20.1-28.3). The objective response rate was 44.4% and Disease Association for the Study of the Liver was 91.1%. Barcelona Clinic Liver Cancer (BCLC) staging significantly affected prognosis, with median PFS for BCLC A, B, C, and D being 19.2, 16.5, 12.1, and 4.8 months, respectively (log-rank P = .016). Median PFS for first-, second-, and third-line treatments were 17.1, 12.6, and 3.2 months, respectively (log-rank P < .001). Patients with positive node expression had significantly shorter PFS (5.1 vs 9.9 months, HR = 2.89, P = .005) and OS (14.9 vs 25.0 months, HR = 3.24, P = .002) compared to those with negative node expression. No grade 5 adverse events occurred. TACE combined with tyrosine kinase inhibitor and PD-1inhibitors shows promising efficacy and acceptable safety for advanced HCC. BCLC staging, treatment line and node status significantly affect outcomes, with earlier intervention yielding greater survival benefit. These exploratory findings from a small retrospective single-arm study require confirmation in larger prospective trials.