Reference Detail

Ref Type

Journal Article

PMID

(32332018)

Authors

Sun W, Li SC, Xu L, Zhong W, Wang ZG, Pan CZ, Li J, Jin GZ, Ta N, Dong W, Liu D, Liu H, Wang HY, Ding J

Title

High FLT3 Levels May Predict Sorafenib Benefit in Hepatocellular Carcinoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research			2020 Apr 24	4302-4312	Clin Cancer Res

URL

Abstract Text

To identify a predictive biomarker of sorafenib for hepatocellular carcinoma personalized therapy.The patients treated with or without sorafenib after hepatocellular carcinoma recurrence from multicenters were matched with propensity score matching analysis. The expression levels of Fms-like tyrosine kinase 3 (FLT3) in hepatocellular carcinoma specimens of the matched patients (n = 276) were analyzed by IHC. The optimal cut-off point of FLT3 levels for overall survival (OS) was defined via Cutoff Finder. Subgroup analysis of OS was employed to investigate the association between FLT3 levels and sorafenib benefit. The predictive value was assessed via Cox regression models with an interaction term. Hepatocellular carcinoma and paratumoral normal tissues were used to investigate the expression and copy-number variation of FLT3. Patient-derived xenograft (PDX) models were used to confirm the association between FLT3 levels and sorafenib response.Patients with FLT3-high hepatocellular carcinoma exhibited a superior OS upon sorafenib treatment. High FLT3 levels were predictive of sorafenib benefit in terms of OS (Pinteraction = 0.00006). Copy-number losses and decreased expression of FLT3 in hepatocellular carcinoma were detected in about 64% of patients. Moreover, the PDXs derived from tumors with high FLT3 levels also displayed a better response to sorafenib.Sorafenib may be able to delay tumor progression in patients with FLT3-high hepatocellular carcinoma. This potential biomarker needs to be further validated in independent cohorts prior to helping stratify patients for precision therapy in advanced hepatocellular carcinoma.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FLT3 over exp	hepatocellular carcinoma	sensitive	Sorafenib	Preclinical - Pdx	Actionable	In a preclinical study, Nexavar (sorafenib) inhibited tumor growth and reduced the percentage of tumor cells expressing Ki-67 in patient-derived xenograft (PDX) models of hepatocellular carcinoma harboring FLT3 overexpression, but had no effect on tumor growth inhibition or Ki-67 expression compared to control treatments in PDX models of HCC harboring decreased FLT3 expression (PMID: 32332018).	32332018
FLT3 over exp	hepatocellular carcinoma	sensitive	Sorafenib	Clinical Study	Actionable	In an observational clinical study, hepatocellular carcinoma patients harboring FLT3 overexpression treated with Nexavar (sorafenib) demonstrated improved overall survival (24.9 months (n=67)) when compared to patients with FLT3 overexpression who received a control treatment (10.0 months (n=49)) or patients with decreased FLT3 expression treated with Nexavar (sorafenib) (16.0 months (n=71)) (PMID: 32332018).	32332018