Clinical Trials in Hepatocellular Carcinoma: An Update

Abstract

The success of sorafenib has spurred an explosive increase of clinical trials testing novel molecular targets and other agents in the treatment of hepatocellular carcinoma (HCC). The paradigm of the studies has been characterized by three noticeable changes. First, the molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for advanced HCC treatment. Agents targeting EGFR, FGFR, PI3K/Akt/mTOR, TGF-β, c-Met, MEK, IGF signaling, and histone deacetylase have been actively explored. Second, the target indication has shifted from advanced stage to early or intermediate stages of disease. The feasibility of combining locoregional therapies and targeted agents, and the use of novel agents after curative treatments are currently under active investigation. Finally, the therapeutic strategy has shifted from monotherapy to combination targeted therapy. We aim to provide a comprehensive overview of newly disclosed and ongoing clinical trials for the treatment of HCC.

Advances in targeted therapies for hepatocellular carcinoma in the genomic era

“…Therapies targeting epigenetic modifiers, such as DNA methyltransferases or histone deacetyl ases, are an attractive approach. 133 A phase I trial of the histone deacetylase inhibitor vorinostat for treatment of patients with HCC is currently being developed, and a phase II trial investi gating another histone deacetyl ase inhibitor, belinostat, detected modest antitumour activity in 42 patients with HCC. 134 A subgroup analysis of 38 patients showed that those with high immuno reactivity to the UV excision repair protein RAD23 homologue B (HR23B)-a reported predictive response biomarker to HDAC inhibitors 135 -had a higher rate of disease stabilization.…”

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

“…These advances have led to the development of targeted therapies in HCC [9][10][11] . Nevertheless, only sorafenib, a multikinase inhibitor, remains till date the sole approved drug in advanced HCC, based on the clinical benefit observed in properly selected patients enrolled in clinical trials [12,13] .…”

FOLFOX4 as First Line Treatment in Advanced Hepatocellular Cancer, when Sorafenib is not Available: Can it be an Option?

“…For example codrituzumab [5], Linifarib, Sunitinib, Brivanib , cixutumumab [6][7][8][9], Everolismus showed no significant increase in overall survival (OS). Only Sorafenib as shown in the SHARP (1) trial in the West and as shown in Oriental trial conducted in the East showed statistically significant (3 months) increase in OS [10][11][12][13][14].…”