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Review
. 2024 May 7:13:104.
doi: 10.12688/f1000research.145493.2. eCollection 2024.

Hepatocellular carcinoma: Advances in systemic therapies

Trevor Kwan-Hung Wu  1 , Rex Wan-Hin Hui  1 , Lung-Yi Mak  1   2 , James Fung  1   2 , Wai-Kay Seto  1   2   3 , Man-Fung Yuen  1   2
Affiliations
Review

Hepatocellular carcinoma: Advances in systemic therapies

Trevor Kwan-Hung Wu et al. F1000Res. .

Abstract

Advanced hepatocellular carcinoma (HCC) is traditionally associated with limited treatment options and a poor prognosis. Sorafenib, a multiple tyrosine kinase inhibitor, was introduced in 2007 as a first-in-class systemic agent for advanced HCC. After sorafenib, a range of targeted therapies and immunotherapies have demonstrated survival benefits in the past 5 years, revolutionizing the treatment landscape of advanced HCC. More recently, evidence of novel combinations of systemic agents with distinct mechanisms has emerged. In particular, combination trials on atezolizumab plus bevacizumab and durvalumab plus tremelimumab have shown encouraging efficacy. Hence, international societies have revamped their guidelines to incorporate new recommendations for these novel systemic agents. Aside from treatment in advanced HCC, the indications for systemic therapy are expanding. For example, the combination of systemic therapeutics with locoregional therapy (trans-arterial chemoembolization or stereotactic body radiation therapy) has demonstrated promising early results in downstaging HCC. Recent trials have also explored the role of systemic therapy as neoadjuvant treatment for borderline-resectable HCC or as adjuvant treatment to reduce recurrence risk after curative resection. Despite encouraging results from clinical trials, the real-world efficacy of systemic agents in specific patient subgroups (such as patients with advanced cirrhosis, high bleeding risk, renal impairment, or cardiometabolic diseases) remains uncertain. The effect of liver disease etiology on systemic treatment efficacy warrants further research. With an increased understanding of the pathophysiological pathways and accumulation of clinical data, personalized treatment decisions will be possible, and the field of systemic treatment for HCC will continue to evolve.

Keywords: Adjuvant; HCC; ICI; Liver; Neoadjuvant; Systemic therapy; TKI.

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Conflict of interest statement

Competing interests: MF Yuen is an advisory board member and/or received research funding from AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals; and received research funding from Arrowhead Pharmaceuticals, Fujirebio Incorporation and Sysmex Corporation. WK Seto received speaker’s fees from AstraZeneca, is an advisory board member and received speaker’s fees of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The remaining authors have no conflict of interests.

Figures

Figure 1.
Figure 1.. Molecular targets of systemic therapy in hepatocellular carcinoma.
See this image and copyright information in PMC

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