Plasma Biomarkers as Predictors of Outcome in Patients with Advanced Hepatocellular Carcinoma

Abstract

Purpose: 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. Experimental Design: 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. Results: 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). Conclusions: 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. Clin Cancer Res; 18(8); 2290–300. ©2012 AACR.

Peripheral blood neutrophil count as a prognostic factor for patients with hepatocellular carcinoma treated with sorafenib

“…Therefore, it is important to identify the best prognostic factors that can predict response to sorafenib. Certain studies showed that serum VEGF concentration and extracellular signal-regulated kinase levels were good predictors (26,27); however, other surrogate biomarkers must be explored to evaluate prognosis or the efficacy of treatment with sorafenib HCC. In the present study, the patients were restricted to those with BCLC stage C or BCLC stage B but who had previously experienced TACE failure, for whom sorafenib is the major treatment method (28).…”

Human and Mouse VEGFA-Amplified Hepatocellular Carcinomas Are Highly Sensitive to Sorafenib Treatment

“…However, patients' response is modest, and sorafenib treatment is associated with side effects (3)(4)(5)(6)(7)(8). Thus, several studies looked for predictive markers for sorafenib response (9)(10)(11), yet no such biomarkers have entered the clinical setting. Predictive biomarkers, identifying patient subsets to guide treatment choices, are usually based on distinct pathogenetic mechanisms, and are the cornerstone of personalized medicine ( 12,13 ).…”

“…10 , 16 ). Although VEGFRs were postulated as mediators of sorafenib response in HCC, testing for VEGF-A serum levels was not found to be predictive of sorafenib treatment success ( 10 ). Moreover, bevacizumab, an antibody against VEGF-A, only shows minimal responses in HCC (17)(18)(19)(20).…”

Elevated Alpha Fetoprotein in Chronic HCV Liver Disease with and without Hepatocellular Carcinoma in Egyptian Patients

“…The incidence of hepatocellular carcinoma (HCC) has rapidly increased in the last decade to reach the sixth most common cancers worldwide (4 ) . The evolution of compensated and decompensated liver cirrhosis has been clearly defined in HCV infected patients (5) . The compensated disease often remains asymptomatic for many years , allowing a normal quality of life .…”