Recent updates in the use of pharmacological therapies for downstaging in patients with hepatocellular carcinoma

ABSTRACT

Introduction

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, but only 20–30% of patients benefit from potentially curative treatments such as liver resection or transplantation. This article reviews conventional treatments and recent progress in pharmacotherapy for advanced HCC, with a focus on downstaging unresectable tumors to resectable status.

Areas covered

In this article, conventional treatments and recent progress in pharmacotherapy for advanced HCC, aiming at downstaging from unresectable to resectable status, are reviewed. Future prospectives of combination therapies using immune checkpoint inhibitors were also introduced by reviewing recent clinical trials, paying attention to the objective response rate as its potential of downstaging treatments.

Expert opinion

The newly developed pharmacological therapies showed higher responses. Although various tumor statuses in advanced HCC hamper detailed analysis of successful conversion rate, the novel combined immunotherapies are expected to provide more opportunities for subsequent curative surgery for initially unresectable advanced HCC. The conversion treatment strategies for unresectable HCC should be separately discussed for ‘technically resectable but oncologically unfavorable’ HCC and metastatic or invasive HCC beyond curative surgical treatments. The optimal downstaging treatment strategy for advanced HCC is awaited. Elucidation of preoperatively available factors that predict successful downstaging will allow the tailoring of promising initial treatments leading to conversion surgery.

Keywords:

• Hepatocellular carcinoma
• downstaging therapies
• immune checkpoint inhibitor
• liver transplantation
• liver resection

Article highlights

• Conventional non-surgical treatments for advanced HCC, including transcatheter chemoembolization, hepatic artery infusion chemotherapy, and systemic chemotherapy using cytotoxic agents, showed limited objective response rates.

• Molecular targeted therapy, such as multikinase inhibitors, angiogenic agents, or EGFR inhibitors, have provided primarily stable disease and rarely downstaged advanced HCC.

• Recent pharmacological therapies, such as lenvatinib, atezolizumab plus bevacizumab, or durvalumab plus tremelimumab, showed a high objective response rate of up to 30%.

• An increasing number of case reports showing successful conversion surgery for metastatic or technically unresectable HCC using immune checkpoint inhibitor drugs is promoting the discussion of an optimal downstaging treatment strategy.

Declaration of interest

S Kondo has received lecture fee from Eisai, Chugai and Incyte, and received research funding for their insititute from Incyte, Abbie, AstraZeneca, Astellas, Eli Lilly and Eisai. The authors have no other 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 apart from those disclosed.

Reviewer dislcosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.