Retrospective analysis of transarterial chemoembolization or hepatic arterial infusion chemotherapy combined with lenvatinib with or without PD-1 inhibitor as first-line therapy for unresectable hepatocellular carcinoma with high tumor burden: a propensity score-matched study.

[PURPOSE] To compare the efficacy, safety, and hepatic impact of TACE or HAIC plus lenvatinib with or without PD-1 inhibitors in unresectable hepatocellular carcinoma with high tumor burden (HTB-uHCC).

[PATIENTS AND METHODS] This retrospective study (2019-2023) included 278 HTB-uHCC patients (defined as tumors exceeding the up-to-11 criteria or exhibiting Vp4 portal vein tumor thrombus) receiving either doublet therapy (TACE or HAIC + lenvatinib, THL) or triplet therapy (TACE or HAIC + lenvatinib + PD-1 inhibitor, THLP) (139 per cohort after 1:1 propensity score matching; caliper=0.2). Primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints comprised objective response rate (ORR), serial liver function tests, and adverse events (AEs).

[RESULTS] The THLP group demonstrated superior OS (median22.4 vs. 17.6 months, HR = 0.55, P < 0.001), PFS (13.5 vs. 8.5 months, HR = 0.53, P < 0.001), and ORR (72.7% vs. 52.5%, P < 0.001) compared to the THL group. No intergroup differences in albumin-bilirubin (ALBI) scores were observed at baseline or during months 1-5 (all P > 0.05). Both cohorts showed significant ALBI deterioration at progression versus baseline (P < 0.001). Child-Pugh stability at 6 months independently predicted ORR (adjusted OR 8.71, 95% CI 4.93-15.40; P <0.001). Grade 3-4 AEs occurred at comparable rates (46.8%vs. 43.2%,P=0.629), with no treatment-related deaths.

[CONCLUSION] Triplet therapy significantly improves survival and tumor response without accelerating early liver function decline in patients with HTB-uHCC. Child-Pugh stability correlates strongly with treatment efficacy.