Comparative Analysis of Lenvatinib and Hepatic Arterial Infusion Chemotherapy in Unresectable Hepatocellular Carcinoma: A Multi-Center, Propensity Score Study

Abstract

The comparative efficacy and safety between lenvatinib and hepatic artery infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) is still unclear. This multicenter historical cohort study enrolled 244 patients who were treated with HAIC (n = 173) or lenvatinib (n = 71) between 2012 and 2020. Propensity score matching (PSM) was performed, and 52 patients were selected per group. Clinical outcomes and safety were compared. Objective response rate (ORR) was not different between the two groups (26.0% vs. 23.1%, p = 0.736). Before PSM, the HAIC group had a higher proportion of Child-Pugh B and portal vein tumor, whereas the lenvatinib group had more patients with extrahepatic metastases, which was adjusted after PSM. There were no differences in progression-free survival (PFS) and overall survival (OS) after PSM (HAIC vs. lenvatinib, median PFS, 3.6 vs. 4.0 months, p = 0.706; median OS 10.8 vs. 7.9 months, p = 0.106). Multivariate Cox-regression showed that alpha-fetoprotein ≤1000 ng/mL was only an associated factor for OS after PSM in all patients (hazard ratio = 0.421, p = 0.011). Subgroup analysis for patients with a high tumor burden beyond the REFLECT eligibility criteria revealed that the HAIC group (n = 29) had a significantly longer OS than did the lenvatinib group (n = 30) (10.0 vs. 5.4 months, p = 0.004). More patients in the HAIC group achieved better liver function than those in the lenvatinib group at the time of best responses. There was no difference in the incidence of grade 3 and 4 adverse events between the two groups. Therefore, lenvatinib is comparable to HAIC in terms of ORR and OS in unresectable HCC meeting REFLECT eligibility criteria.

Analysis on Efficacy of Hepatic Artery Infusion Chemotherapy with or without Lenvatinib for Unresectable Hepatocellular Carcinoma

“…Overall, combination therapy of HAIC and lenvatinib had good safety and efficacy for unresectable HCC patients. With regard to post-treatment liver function, worse residual liver function was detected in the combination therapy group versus the HAIC group in our study (11.10% vs. 50.00%), which was also verified by Lee et al [29]. Therefore, in HCC patients with poor liver function, combination therapy may still not be the treatment that can improve their survival.…”

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

“… 883 In a multicenter retrospective observational study conducted in South Korea, HAIC was compared to lenvatinib in 244 patients with advanced HCC, and the results showed no difference in the OS between the HAIC and lenvatinib group (9.4 vs. 9.3 months, P =0.489). 884 …”

Factors associated with the survival outcomes of patients with untreated hepatocellular carcinoma: An analysis of nationwide data

“…HBV infection was confirmed by HBsAg positivity, HCV infection was confirmed by the presence of anti-HCV antibody (Ab) positivity, and HBV+HCV infection was confirmed by both HBsAg and anti-HCV Ab positivity. The initial serum AFP levels were dichotomized into ≥1000 ng/mL and <1000 ng/mL based on a previous study regarding factors predictive of "advanced" HCC (14)(15)(16). KPLCR is based on a national cancer registry program, in which all registered patients' dates of death are recorded.…”