Systemic therapy for hepatocellular carcinoma: current status and future perspectives

Area of Science:

• Hepatobiliary cancers
• Medical oncology
• Translational medicine

Background:

• Sorafenib was the standard for advanced hepatocellular carcinoma (HCC).
• Lenvatinib showed non-inferiority to sorafenib, becoming another standard of care.
• Atezolizumab plus bevacizumab demonstrated superior overall survival and progression-free survival over sorafenib for first-line therapy.

Purpose of the Study:

• To review current systemic therapies for advanced HCC.
• To identify unmet needs in HCC treatment, including sequential therapy and treatment for Child-Pugh class B patients.
• To emphasize the need for well-designed clinical trials.

Main Methods:

• Review of clinical trial data and established treatment guidelines for advanced HCC.
• Analysis of efficacy and safety profiles of various systemic agents.
• Identification of gaps in current treatment paradigms.

Main Results:

• Tyrosine kinase inhibitors (e.g., lenvatinib) and immune checkpoint inhibitors (e.g., atezolizumab plus bevacizumab) are established first-line options.
• Regorafenib, cabozantinib, and ramucirumab show benefit in second-line settings after sorafenib.
• Evidence for sequential treatment post-atezolizumab plus bevacizumab is lacking.
• Effective treatments for Child-Pugh class B HCC patients remain an unmet need.

Conclusions:

• Systemic therapy for advanced HCC has advanced significantly, with multiple effective agents available.
• Critical unmet needs include defining optimal sequential treatment strategies and developing therapies for Child-Pugh class B HCC.
• Further clinical trials are essential to address these remaining challenges and improve patient outcomes.