Analysis of Lenvatinib’s Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma

SIMPLE SUMMARY: With the emergence of the concepts of transarterial chemoembolization (TACE) refractoriness and unsuitability and recent advances in systemic therapy, treatment options for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC) are increasing. However, the efficacy of lenvatinib and its combination with TACE in clinical practice has not yet been adequately investigated. This study investigated the efficacy of lenvatinib and its combination with TACE after lenvatinib in patients with intermediate-stage u-HCC who were mainly judged to be TACE-refractory or -unsuitable. The results demonstrated the efficacy of lenvatinib and confirmed that further improvements in prognosis could be obtained with TACE after lenvatinib induction. In the intermediate-stage u-HCC, the results suggest it may be important to consider not only the use of lenvatinib but also its combination with TACE to improve patients’ prognosis further, even if they are deemed TACE-refractory or -unsuitable. ABSTRACT: Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin–bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.