Tumor Fibroblast Growth Factor Receptor 4 Level Predicts the Efficacy of Lenvatinib in Patients With Advanced Hepatocellular Carcinoma.

Clinical and Translational Gastroenterology
Masami YamauchiKazuaki Chayama

Abstract

Biomarkers for optimizing the outcome of treatment with lenvatinib in patients with advanced hepatocellular carcinoma remain to be established despite intensive and comprehensive genomic research. Lenvatinib is characterized by its prominent inhibitory potency for fibroblast growth factor receptor (FGFR) 4 compared with earlier tyrosine kinase inhibitors. Thus, in this study, we focused on simplified quantification of FGFR4 in tumors as a potential predictive indicator. According to The Cancer Genome Atlas data set curation, FGFR4 messenger RNA is broadly overexpressed in hepatocellular carcinoma in the absence of gene alteration. Gene set enrichment analysis revealed that the aggressiveness of the tumor was closely related to the FGFR4 level. To confirm the relationship between the benefits of lenvatinib and tumor addiction to the FGFR4 pathway, we analyzed protein levels in tumors and peripheral blood obtained from 57 prospectively registered patients treated with lenvatinib. Positive immunohistochemistry (>10% of tumor cells) for FGFR4 in biopsy samples before treatment was associated with a longer progression-free survival (2.5 vs 5.5 months, P = 0.01) and a favorable objective response rate (31% vs 81%, P = 0.006). By cont...Continue Reading

References

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
biopsies
ELISA

Software Mentioned

Gene Set Enrichment Analysis
R
OncoLnc
mRECIST
GenePattern

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