Efficacy and Safety of Lenvatinib Plus Programmed Death-1 Inhibitors with or Without Transarterial Chemoembolization in the Treatment of Unresectable Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2024 Nov 25:11:2309-2320. doi: 10.2147/JHC.S485047. eCollection 2024.

Abstract

Purpose: Transarterial chemoembolization (TACE) is recommended as a standard therapy for intermediate-stage hepatocellular carcinoma (HCC) and is the most widely used first-line treatment for advanced HCC. This study aimed to evaluate the clinical benefits and tolerability of TACE added to a combination of lenvatinib and programmed death-1 (PD-1) inhibitor in patients with unresectable HCC (uHCC).

Patients and methods: We conducted a retrospective cohort study involving 144 patients with uHCC treated between August 2020 and August 2023. Patients received a combination of lenvatinib and a PD-1 inhibitor with or without TACE (T+L+P, n=81 or L+P, n=63, respectively). The baseline characteristics of the two groups were compared, and propensity score matching (PSM) was used to minimize bias. The study endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Factors influencing survival rates were analyzed using Cox regression, and adverse events (AEs) were documented and assessed.

Results: Before PSM, the T+L+P group showed significantly higher ORR (64.1% vs 44.4%, p < 0.05), longer median PFS (14.3 vs 9.6 months, p < 0.05), and longer median OS (24.6 vs 19.5 months, p < 0.05) compared to the L+P group. Even post-PSM, the T+L+P group showed significantly better OS and PFS compared to the L+P group (mOS: 28.0 vs 17.6 months p=0.0011, mPFS: 15.8 vs 9.3 months, p < 0.05). Univariate and multivariate analyses identified treatment options as independent factors for PFS and OS. The safety profile of the T+L+P regimen was acceptableThe incidence and severity of adverse reactions in the T+L+P group were not significantly different compared to the L+P group (any grade, 90.1 vs 93.6%, p=0.551; grade≥3, 25.9 vs 23.8%, p=0.843).

Keywords: PD-1 inhibitor; combination therapy; lenvatinib; propensity score matching; transarterial chemoembolization; unresectable hepatocellular carcinoma.

Grants and funding

This study was financially supported by the Guangxi Medical and health key discipline construction project, Guangxi medical and healthcare appropriate technology development and promotion and application projects (grant number: S2022132), Guangxi Natural Science Foundation (grant number: 2022JJA140009) and Self-financed scientific research projects of Guangxi Autonomous Region Health and Wellness Commission(Z-C20230840).