Oral chemotherapy for the treatment of hepatocellular carcinoma

ABSTRACT

Introduction: Many clinical trials have been conducted with chemotherapies in patients with advanced hepatocellular carcinoma (HCC). However, few agents have shown efficacy. It is thought that the efficacy of some agents might have resulted from the heterogeneity of tumors, insufficient dosages due to liver cirrhosis, and post-therapy effects. In recent years, immune checkpoint inhibitors have shown promising clinical activity and safety in patients with advanced HCC.

Areas covered: The authors provide an overview of chemotherapies used for the treatment of HCC, including ongoing trials. The authors also provide their expert opinion on the subject area and provide their future perspectives.

Expert opinion: Based on favorable phase III clinical trial data, sorafenib and lenvatinib are considered promising agents for HCC as first-line systemic chemotherapy. Moreover, regorafenib and cabozantinib are useful second-line therapies after the failure of sorafenib. Furthermore, in early phase clinical trials, immune checkpoint inhibitors and the combinations of these inhibitors and molecular targeted agents have demonstrated promising activity. Therefore, better survival results are expected from future phase III clinical trials.

KEYWORDS:

• Hepatocellular carcinoma
• immune checkpoint inhibitor
• multikinase inhibitor
• oral chemotherapy
• sorafenib

Article highlights

• Immune checkpoint inhibitors show promising clinical activities and safety in patients with advanced hepatocellular carcinoma (HCC).

• Based on the favorable data from phase III clinical trials, sorafenib and lenvatinib are promising agents for HCC as first-line systemic chemotherapy.

• Sorafenib only became an oral chemotherapy for advanced HCC quite recently; therefore, there were no effective alternative chemotherapies after disease progression on sorafenib.

• Regorafenib and cabozantinib are useful as the second-line therapy after the failure of sorafenib.

• Combinations of these inhibitors and molecular targeted agents have also shown promising activities.

• In the future, we expect better results on survival from phase III trials.

This box summarizes key points contained in the article.

Declaration of interest

S Kondo has received research funding from AstraZeneca, Eli Lilly Japan K.K., ASLAN, Pfizer Inc, Takeda Yakuhin, Ltd., and Bayer Yakuhin, Ltd. 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. One referee has consulted and or acted in an advisory role for Eli Lilly and Company, Bayer Healthcare, ArQule, Ipsen, and Exelixis. They have also received honoraria from AstraZeneca.

Additional information

Funding

This manuscript was not funded.