Addition of Intra-Arterial Therapy to Immunotherapy Improves Outcomes in Unresectable Hepatocellular Carcinoma: Taiwan Multicenter Cohort Study.

INTRODUCTION

Evidence supporting the combination of immunotherapy with intra-arterial therapy (IAT) for unresectable hepatocellular carcinoma (HCC) remains limited. This study aimed to evaluate whether the addition of IAT to first-line immunotherapy improves survival outcomes.

METHODS

Using the Taiwan Liver Cancer Association (TLCA) Research Group database, we identified patients with unresectable HCC who initiated first-line immunotherapy between May 2017 and January 2024. Patients with Barcelona Clinic Liver Cancer (BCLC) stage A or D disease, prior liver transplantation, or follow-up of <6 weeks were excluded. Eligible patients received either IAT (transarterial chemoembolization, radioembolization, or hepatic arterial infusion chemotherapy) at the initiation of immunotherapy or immunotherapy alone. After 1:3 propensity score matching, 90 and 270 patients were included in the IAT and control groups, respectively. Overall survival (OS) was analyzed using adjusted hazard ratios (aHRs) in a time-dependent model.

RESULTS

The IAT group achieved a higher objective response rate (46.7% vs. 26.3%; p < 0.001) and a longer duration of response (median 19.0 [IQR: 9.7-36.6] vs. 11.0 [IQR: 8.4-23.1] weeks; p = 0.009) than the control group. IAT was independently associated with improved OS (aHR 0.53, 95% CI: 0.37-0.75; p < 0.001). Factors associated with worse OS included Child-Turcotte-Pugh class B (aHR 1.41, 95% CI: 1.01-1.97; p = 0.042), albumin-bilirubin grade >1 (aHR 1.58, 95% CI: 1.11-2.27; p = 0.012), tumor burden beyond the up-to-7 criteria (aHR 1.67, 95% CI: 1.02-2.74; p = 0.043), and portal vein invasion (aHR 1.67; 95% CI: 1.19-2.35; p = 0.003). Five-year OS was higher in the IAT group than in the control group (28.7% [95% CI: 17.8-46.2] vs. 16.4% [95% CI: 10.7-25.2]; p = 0.007). Landmark and subgroup analyses consistently supported the OS benefit of IAT.

CONCLUSION

In unresectable HCC, the addition of IAT to first-line immunotherapy improves response rates, prolongs the duration of response, and enhances OS.