Frontline therapy for advanced hepatocellular carcinoma: an update

Area of Science:

• Hepatology and Oncology
• Cancer Research
• Clinical Therapeutics

Background:

• Hepatocellular carcinoma (HCC) is the fastest-growing cause of cancer mortality in the US, with increasing incidence linked to cirrhosis, hepatitis B, hepatitis C, and nonalcoholic steatohepatitis (NASH).
• Over half of HCC patients present with advanced disease, necessitating effective systemic therapies.
• Current frontline options include sorafenib, lenvatinib, and atezolizumab/bevacizumab, with recent advances improving survival outcomes.

Purpose of the Study:

• To review the evolving landscape of frontline systemic therapy for advanced Hepatocellular Carcinoma (HCC).
• To discuss emerging treatment strategies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs).
• To highlight unmet needs in identifying predictive biomarkers and defining treatment for specific HCC subgroups.

Main Methods:

• Review of recent clinical trials and therapeutic advancements in advanced HCC.
• Analysis of current frontline systemic therapy options and their efficacy.
• Discussion of ongoing research and future directions in HCC treatment.

Main Results:

• Significant survival improvements have been observed with recent first-line treatments like atezolizumab/bevacizumab (median overall survival 19.2 months).
• The combination of durvalumab and tremelimumab shows promise as a potential new frontline option based on Phase III HIMALAYA trial results.
• Multiple clinical trials are investigating novel agents and combinations, including ICI-based therapies, for frontline treatment.

Conclusions:

• The frontline treatment for advanced HCC is rapidly evolving, with a shift towards immunotherapy and combination therapies.
• Identifying predictive biomarkers for ICI- and TKI-based therapies remains a critical unmet need.
• Further research is required to define optimal treatment strategies for specific HCC populations, such as Child-Pugh B and post-transplant recurrent HCC.