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Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment
1Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea.
Abstract:
Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate second-line systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.
Insights
This review examines second-line systemic agents for hepatocellular carcinoma (HCC). It highlights approved therapies and discusses considerations for selecting optimal treatments after initial systemic therapy failure.
Area of Science:
- Hepatobiliary cancers
- Medical oncology
- Pharmacotherapy
Background:
- Hepatocellular carcinoma (HCC) treatment has been limited, with sorafenib as the sole approved systemic agent for nearly a decade.
- While newer agents like regorafenib, cabozantinib, and ramucirumab show improved survival, and immune checkpoint inhibitors are emerging, optimal selection of second-line therapy remains unclear.
Purpose of the Study:
- To review current and future perspectives on second-line systemic agents for hepatocellular carcinoma (HCC).
- To address the limited knowledge regarding considerations for selecting appropriate second-line systemic agents in HCC management.
Main Methods:
- Literature review of clinical trials and approved therapies for HCC.
- Analysis of systemic agents used as second-line treatment following initial therapy failure.
Main Results:
- Regorafenib, cabozantinib, and ramucirumab have demonstrated improved overall survival in phase III trials.
- Immune checkpoint inhibitors (nivolumab, pembrolizumab) are available for sorafenib-refractory HCC in some regions.
Conclusions:
- Several systemic agents are now available for second-line treatment of HCC, offering improved outcomes.
- Further research is needed to establish clear guidelines for selecting the most effective second-line systemic agent based on patient characteristics and prior treatment.
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