Review article: systemic treatment of hepatocellular carcinoma

Area of Science:

• Hepatobiliary cancers
• Medical oncology
• Translational research

Background:

• Sorafenib, a tyrosine kinase inhibitor, was the first systemic therapy to demonstrate survival benefit for advanced hepatocellular carcinoma (HCC) in 2007.
• Despite initial success, numerous targeted therapies failed in early clinical trials for HCC.
• A decade passed before additional tyrosine kinase inhibitors showed efficacy in Phase III trials.

Purpose of the Study:

• To provide a comprehensive overview of the advancements in systemic therapy for hepatocellular carcinoma.
• To highlight the evolution of targeted therapies and the emergence of immunotherapy in HCC treatment.

Main Methods:

• Literature review of recently published studies.
• Analysis of data presented at recent scientific meetings.
• Systematic search using keywords: hepatocellular carcinoma, tyrosine kinase inhibitors, immunotherapy, immune checkpoint inhibitors, sorafenib, regorafenib, lenvatinib, cabozantinib, ramucirumab, and nivolumab.

Main Results:

• Discusses the progression of targeted therapies for HCC since sorafenib's approval, including both therapeutic failures and recent breakthroughs.
• Highlights the critical need for biomarkers to personalize treatment strategies in HCC.
• Explores the growing role and potential of immunotherapy in managing hepatocellular carcinoma.

Conclusions:

• Sorafenib and regorafenib are approved first- and second-line treatments for HCC, respectively.
• Nivolumab has received conditional approval for sorafenib-experienced HCC patients in the US.
• Lenvatinib, cabozantinib, and ramucirumab have shown promise in Phase III trials, potentially expanding future HCC treatment options.