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The Treatment Landscape of Advanced Hepatocellular Carcinoma

  • Gastrointestinal Cancers (J Meyer, Section Editor)
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Abstract

Purpose of review

The systemic treatment of advanced hepatocellular carcinoma (HCC) has significantly evolved. Immune checkpoint inhibitors (ICIs) have demonstrated clinical efficacy and more favorable toxicity profiles compared to multikinase inhibitors. Combination therapy with ICIs may provide greater anti-tumor activity compared to ICI monotherapy. This review will discuss the current treatment landscape of advanced HCC, with a focus on recently completed and ongoing trials of ICI combinations, as well as future directions. 

Recent findings

Atezolizumab/bevacizumab has been approved as first-line therapy in patients with advanced HCC based on its superiority over sorafenib in the pivotal IMbrave150 trial. Similarly, durvalumab/tremelimumab demonstrated an improvement in overall survival compared to sorafenib in the HIMALAYA trial. Other combinations of ICIs with targeted agents and dual immune checkpoint blockade are currently being investigated in large randomized Phase 3 trials for the first-line treatment of HCC.

Summary

Results of several ICI combination trials have been reported or are anticipated in the next few years and may potentially expand the therapy options in this patient population. Further areas of exploration include the use of ICIs in earlier stages of disease, other immunotherapy approaches such as adoptive T cell therapy, and the identification of predictive biomarkers. These ongoing efforts will likely further improve patient outcomes in the future.

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Authors and Affiliations

  1. Department of Medical Oncology, Division of Medicine, University of Washington, Seattle, WA, 98109, USA

    Kit Man Wong, Gentry G. King & William P. Harris

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Conflict of Interest

Kit Man Wong has received institutional research funding from Genentech, Exelixis, Shanghai De Novo Pharmatech, Adaptimmune Therapeutics, Pfizer, Astellas, Replimune, Mitsubishi Tanabe Pharma, Eli Lilly, and AstraZeneca and has received compensation for participation on advisory boards from Genentech, Exelixis, and HalioDX. Gentry G. King has received institutional funding for clinical trials from Bayer; has received compensation for service as a consultant from Zymeworks and Tempus; has received compensation for participation on advisory boards from Pfizer and QED Therapeutics; has received speaker’s honoraria from the Society for Immunotherapy of Cancer (SITC) and the International Society of Gastrointestinal Oncology (IGSIO); received reimbursement for travel/accommodations from the IGSIO; is member of the National Cancer Institute (NCI) Hepatobiliary Task Force and Southwest Oncology Group; and is Co-Chair of the ctDNA GI Steering Committee. William P. Harris has received institutional research funding from Exelixis, Bristol-Myers Squibb, MedImmune, AstraZeneca, Bayer, Boston Scientific, Merck, Koo Foundation, and Zymeworks; has received compensation for service as a consultant from Zymeworks, Merck, and BD Medical; has received compensation for participation on advisory boards from Exelixis, AstraZeneca, and Eisai; and serves on the Board of Directors (unpaid) of the GI Cancers Alliance.

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Wong, K.M., King, G.G. & Harris, W.P. The Treatment Landscape of Advanced Hepatocellular Carcinoma. Curr Oncol Rep 24, 917–927 (2022). https://doi.org/10.1007/s11912-022-01247-7

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