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Therapeutic Efficacy and Safety of Lenvatinib for Unresectable Hepatocellular Carcinoma Beyond Progression with Sorafenib

Authors :
Yasuhiro Mitsui
Tetsuji Takayama
Katsuhisa Horimoto
Naoki Muguruma
Masahiro Sogabe
Harumi Kagiwada
Yasuteru Fujino
Takahiro Tanaka
Masashi Kitazawa
Hiroshi Miyamoto
Tatsuya Taniguchi
Koichi Okamoto
Kazuhiko Fukui
Yasushi Sato
Tetsu Tomonari
Hironori Tanaka
Akihiro Hirao
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

Background & AimsThe efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway by protein array analysis.MethodsWe retrospectively enrolled 57 unresectable HCC patients. Radiologic responses in 53 patients were evaluated by modified Response Evaluation Criteria in Solid Tumors. Active signal transduction pathways in cells were identified by protein array analysis, including 1205 proteins.ResultsPatients comprised 34 tyrosine kinase inhibitor (TKI)-naive (first-line), nine SOR-intolerant (second-line), and ten resistant to regorafenib (third-line). Objective response rates (ORRs) were 61.8% (21/34) in TKI-naive, 33.3% (3/9) in second-line, and 20.0% (2/10) in third-line groups. The overall survival (OS) and the progression free survival (PFS) in the first-line was significantly longer than those in third-line group (p50 value of LEN against PLC/PRF5-R2 cells (30 μM) was significantly higher than that against PLC/PRF5 cells (6.4 μM). LEN inhibited significantly more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than PLC/PRF5-R2 cells.ConclusionsLEN was active and safe as a second/third-line treatment for unresectable HCC. LEN seems to be more effective for HCC patients with better hepatic reserve function or before TKI-resistance is acquired because of partial cross-resistance to SOR.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....2932383dbffaf4e62fda8f32db01f6c0
Full Text :
https://doi.org/10.1101/2020.01.03.893800