Second-line treatment options for hepatocellular carcinoma: current state and challenges for the future

ABSTRACT

Introduction

Since the approval of sorafenib for systemic treatment of advanced hepatocellular carcinoma (HCC), many tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown efficacy and tolerability as first-line treatments. On the other hand, these first-line therapies are associated with low objective response and drug resistance. Many drugs have been successfully tested for second-line treatment of advanced HCC. While the rapid proliferation of second-line treatments for advanced HCC brings hope to patients, it also complicates clinical decision-making.

Areas covered

This review aims to facilitate decisions by summarizing the latest guidelines for second-line treatment of HCC in various countries or regions. We then review existing second-line treatment options and discuss challenges that should be addressed in the future. A literature search was conducted in April 2022 of PubMed/Medline, Cochrane library, and abstracts of international cancer meetings.

Expert opinion

There is no standard second-line treatment, especially for the case of sequential treatment after atezolizumab plus bevacizumab (atezo+bev) and further studies focused on sequential treatment are warranted in this setting. The design of clinical trials, different etiologies, and complications or quality of life (QoL) are interesting issues in the second-line setting.

KEYWORDS:

• Hepatocellular carcinoma
• systemic treatment
• second-line
• adverse event
• tyrosine kinase inhibitor
• immune checkpoint inhibitor

Article highlights

• Atezo+bev recently supplanted sorafenib as the new standard first-line treatment for patients with advanced HCC.

• Many drugs, TKIs or ICIs, have demonstrated improved outcomes for second-line treatment of advanced HCC and recommended for second-line setting by various countries or regions.

• The lack of data of subsequent therapy after atezo+bev is a major weakness in the literature, and further studies are needed to assess sequential treatment in this setting.

• Future studies identifying and evaluating the design of clinical trials, different etiologies, and complications or QoL in the second-line setting are expected to improve patient selection survival time.

This box summarizes key points contained in the article.

Acknowledgments

We thank the authors of the cited references for their excellent work. We also thank the Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, and the Ministry of Education, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University.

Author contributions

Conception and design of the study: JHZ. Drafting of the manuscript and analysis of data: JHZ, LL, HTL, GLZ, ZJD. Critical revision of the manuscript for important intellectual content: JHZ, HTL. All authors participated in data analysis, read the manuscript and approved the final version to be published. JHZ had full access to all the data in the study and serves as guarantor, taking full responsibility for the integrity of the data and the accuracy of the data analysis.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer has received honoraria from Roche, Bayer, Eisai, MSD, BMS, AstraZeneca, Ipsen, and one reviewer is paid by Eisai Co., Ltd. for attending meetings. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose

Additional information

Funding

This work was supported by the Specific Research Project of Guangxi for Research Bases and Talents (GuiKe AD22035057), the National Natural Science Foundation of China (82060510 and 82260569), and the Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Gaungxi Medical University), Ministry of Education (GKE-ZZ202217).