Sorafenib in advanced hepatocellular carcinoma

Area of Science:

• Hepatocellular Carcinoma Research
• Oncology Drug Development
• Multikinase Inhibitor Therapy

Background:

• Advanced hepatocellular carcinoma lacks effective systemic therapies.
• Preliminary studies indicated potential efficacy of sorafenib, an oral multikinase inhibitor.
• Sorafenib targets vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and Raf kinases.

Purpose of the Study:

• To evaluate the efficacy and safety of sorafenib compared to placebo in advanced hepatocellular carcinoma.
• To determine the impact of sorafenib on overall survival and time to symptomatic progression.
• To assess the effect of sorafenib on radiologic progression and patient safety.

Main Methods:

• A multicenter, phase 3, double-blind, placebo-controlled trial.
• 602 patients with advanced hepatocellular carcinoma, treatment-naive, were randomized to sorafenib (400 mg twice daily) or placebo.
• Primary endpoints included overall survival and time to symptomatic progression; secondary endpoints included time to radiologic progression and safety.

Main Results:

• Sorafenib demonstrated a median overall survival of 10.7 months versus 7.9 months for placebo (P<0.001).
• Median time to radiologic progression was significantly longer with sorafenib (5.5 months vs. 2.8 months, P<0.001).
• Adverse events such as diarrhea and hand-foot skin reaction were more frequent with sorafenib.

Conclusions:

• Sorafenib significantly increased median survival by nearly 3 months in advanced hepatocellular carcinoma patients.
• The time to radiologic progression was also significantly extended with sorafenib treatment.
• Sorafenib represents a promising systemic therapy option for advanced hepatocellular carcinoma.