Systemic treatment of advanced hepatocellular cancer: new hope on the horizon

ABSTRACT

Introduction: Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality in the world. The majority of the patients present at an advanced or incurable stage where neither locoregional treatment nor combination treatment of locoregional treatment and systemic therapies is feasible. For decades sorafenib was the only treatment option available for advanced HCC. However, with the advent of new and more effective therapies recently, the overall prognosis of advanced HCC has improved significantly.

Areas covered: This review summarises the current systemic treatment options available and future prospects in the management of advanced HCC where patients are not suitable for locoregional treatment.

Expert opinion: New effective targeted therapeutics have dramatically changed the treatment landscape for advanced HCC. The incorporation of sequential therapy including sorafenib or lenvatinib as first-line treatment and immunotherapy, regorafenib or cabozantinib as second-line treatment have significantly improved outcomes for patients with advanced HCC. Further development of novel combinations of these new agents and predictive/prognostic biomarkers are being explored. Efforts should also be made to tailor treatment to individual patients based on etiology, clinical and molecular factors.

KEYWORDS:

• Hepatocellular cancer
• systemic treatment
• molecular targeted agents
• immunotherapy
• biomarkers
• future research

Article highlights

• HCC has a particularly complex molecular and genetic pathogenesis.

• Lenvatinib may serve as an alternative to sorafenib which was the only systemic treatment available over the past decade.

• The second line therapies include regorafenib, immunotherapy or cabozantinib rather than best supportive care.

• Novel combinations of different drugs should be investigated and finding ways to successfully incorporate these combinations in the HCC treatment will be significant.

• Biomarkers and etiology will help to personalize the treatment of patients with HCC.

Declaration of interest

Niall Tebbutt has received honoraria from Roche, Amgen, Merck-Serono, Merck Sharp & Dohme, Bayer, Eisai, and Bristol-Myers Squibb. He has received travel support from Bayer. 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 disclosures

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

Additional information

Funding

This manuscript was not funded.