High FLT3 Levels May Predict Sorafenib Benefit in Hepatocellular Carcinoma

Abstract

Purpose: To identify a predictive biomarker of sorafenib for HCC personalized therapy. Experimental Design: The patients treated with or without sorafenib after HCC recurrence from multi-centers were matched with propensity score matching analysis. The expression levels of FLT3 in HCC specimens of the matched patients (n=276) were analyzed by immunohistochemistry. The optimal cutoff 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. HCC and para-tumoral normal tissues were used to investigate the expression and CNV of FLT3. PDX models were used to confirm the association between FLT3 levels and sorafenib response. Results: HCC patients with high FLT3 levels exhibited a superior OS upon sorafenib treatment. High FLT3 levels were predictive of sorafenib benefit in term of OS (p of interaction=0.00006). Copy number losses and decreased expression of FLT3 in HCC were detected in about 64% of patients. Moreover, the PDXs derived from tumors with high FLT3 levels also displayed a better response to sorafenib. Conclusions: Sorafenib may be able to delay tumor progression in FLT3-High HCC patients. This potential biomarker needs to be further validated in independent cohorts prior to helping stratify patients for precision therapy in advanced HCC.