Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?

Abstract

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.

Using prognostic and predictive clinical features to make personalised survival prediction in advanced hepatocellular carcinoma patients undergoing sorafenib treatment

“…Although such data permits optimisation of the patient groups in whom sorafenib is administered, molecular markers related to the mechanism of action of targeted agents remain an important and, as yet unfulfilled, goal. 29 The inclusion of aetiological factors in our model is clearly justified on the basis of the previously mentioned evidence that HCV positivity is a predictor of survival benefit compared to placebo. However, the inclusion of aetiological factors other than HBV and HCV, which are relatively 'objective' is problematical.…”

Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

“…Several retrospective studies evaluating laboratory and clinical findings during treatment have also identified potential predictive markers of response or resistance to therapy. During treatment with sorafenib, hand‐foot skin reaction, hypertension or diarrhoea have been associated with clinical benefits . Likewise, low neutrophil to lymphocyte ratio, aetiology, extrahepatic spread, high s‐c‐KIT, low baseline hepatocyte growth factor concentration, FGF3/FGF4 amplification and rare vascular endothelial growth factor‐A (VEGF‐A) amplification have also been associated with improved response to sorafenib .…”

HGF/c-Met Axis: The Advanced Development in Digestive System Cancer

“…About 75-85% of primary liver cancer cases are HCC (Siegel and Miller, 2019). Sorafenib [a small-molecule multi-kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFRs) rapidly accelerated fibrosarcoma (RAF) and other protein kinases] has been regarded as the standard of treatment for patients with advanced HCC since 2007 (Marisi et al, 2018). However, survival among patients even after treatment with sorafenib is still low, necessitating urgent development of new and effective treatment methods.…”