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Review
. 2018 Sep;48(6):598-609.
doi: 10.1111/apt.14913. Epub 2018 Jul 23.

Review article: systemic treatment of hepatocellular carcinoma

Matthias Pinter  1   2 , Markus Peck-Radosavljevic  3
Affiliations
Review

Review article: systemic treatment of hepatocellular carcinoma

Matthias Pinter et al. Aliment Pharmacol Ther. 2018 Sep.

Abstract

Background: The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma. Since then many drugs failed in the first- and second-line setting and it took almost another decade until further tyrosine kinase inhibitors succeeded in phase III trials.

Aim: To summarise the evolving field of systemic therapy of hepatocellular carcinoma.

Methods: We reviewed recently published studies identified from PubMed and data presented at recent meetings. Main search terms included hepatocellular carcinoma, tyrosine kinase inhibitors, immunotherapy, immune checkpoint inhibitors, sorafenib, regorafenib, lenvatinib, cabozantinib, ramucirumab, and nivolumab.

Results: We discuss the evolution of targeted therapies since the approval of sorafenib including failures and recent advances. We also elaborate the unmet need of biomarkers to guide treatment decisions and discuss the emerging field of immunotherapy in hepatocellular carcinoma.

Conclusions: The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States. With lenvatinib in the first line, and cabozantinib and ramucirumab in sorafenib-experienced patients, three more targeted therapies reached their primary endpoint in phase III trials and may soon be added to the treatment armamentarium.

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Figures

Figure 1
Figure 1
Candidates for systemic therapy. HCC, hepatocellular carcinoma; EHM, extrahepatic metastases; MVI, macrovascular invasion; PS, Performance Status; TACE, transarterial chemoembolisation
Figure 2
Figure 2
Timeline of targeted therapies that succeeded and failed in phase III randomised controlled trials of hepatocellular carcinoma (years refer to date of press announcement)
See this image and copyright information in PMC

References

    1. Pinter M, Hucke F, Zielonke N, et al. Epidemiological trends of hepatocellular carcinoma in Austria. Dig Dis. 2014;32:664‐669. - PubMed
    1. Hucke F, Sieghart W, Schoniger‐Hekele M, et al. Clinical characteristics of patients with hepatocellular carcinoma in Austria ‐ is there a need for a structured screening program? Wien Klin Wochenschr. 2011;123:542‐551. - PubMed
    1. Pinter M, Trauner M, Peck‐Radosavljevic M, et al. Cancer and liver cirrhosis: implications on prognosis and management. ESMO Open. 2016;1:e000042. - PMC - PubMed
    1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87‐108. - PubMed
    1. European Association for the Study of the Liver . EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182‐236. - PubMed

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