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Clin Cancer Res. 2012 Apr 15;18(8):2290-300. doi: 10.1158/1078-0432.CCR-11-2175. Epub 2012 Feb 28.

Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma.

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Barcelona Clínic Liver Cancer Group, Liver Unit, CIBERehd, Institut d'Investigacions Biomèdiques, August Pi i Sunyer, Hospital Clínic Barcelona, Barcelona, Spain.



Validated biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma (HCC). One of the objectives of the phase III, randomized, controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy.


In SHARP, 602 patients with advanced HCC were randomized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis. Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment. The candidate biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib.


In both the entire patient population and the placebo cohort, baseline angiopoietin 2 (Ang2) and VEGF concentrations independently predicted survival. Clinical variables such as macroscopic vascular invasion, Eastern Cooperative Oncology Group (ECOG) performance status, and baseline α-fetoprotein and alkaline phosphatase concentrations also independently predicted survival in these groups. In the sorafenib cohort, trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline (P of interaction = 0.081 and 0.073, respectively).


The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC. In contrast, none of the biomarkers tested significantly predicted response to sorafenib.

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