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New Opportunities to Individualize Frontline Therapy in Advanced Stages of Hepatocellular Carcinoma

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Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally and is rising in incidence. Until recently, treatment options for patients with advanced stages of HCC have been limited to antiangiogenic therapies with modest improvements in overall survival. The emerging role of immunotherapy with immune checkpoint inhibitors (ICI) in oncology has led to a rapid expansion in treatment options and improvements in outcomes for patients with advanced stages of HCC. Recent clinical trials have shown meaningful survival improvement in patients treated with the combination of bevacizumab and atezolizumab, as well as with the combination of tremelimumab with durvalumab, resulting in regulatory approvals of these regimens as frontline therapy. Beyond improvements in overall survival, ICI-based combination regimens achieve higher rates of durable treatment response than multikinase inhibitors and have favorable side effect profiles. With the emergence of doublet anti-angiogenic and immune checkpoint inhibitor (ICI) and dual ICI combinations, individualized therapy is now possible for patients based on co-morbidity profiles and other factors. These more potent systemic therapies are also being tested in earlier stages of disease and in combination with loco-regional therapies such as trans-arterial chemoembolization and stereotactic body radiotherapy. We summarize these advances and emerging therapeutic combinations currently in clinical trials.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, UC San Francisco, San Francisco, CA, USA

    John D. Gordan, Bridget P. Keenan, Huat Chye Lim & R. Katie Kelley

  2. Quantitative Biosciences Institute, UC San Francisco, San Francisco, CA, USA

    John D. Gordan & Huat Chye Lim

  3. Cancer Immunotherapy Program, Helen Diller Family Comprehensive Cancer Center, UC San Francisco, San Francisco, CA, USA

    Bridget P. Keenan & R. Katie Kelley

  4. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Mark Yarchoan

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Dr. Gordan is supported by a Burroughs Wellcome Fund Career Award.

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Dr. Gordan and Dr. Lim declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Dr. Keenan is a member of the consulting/advisory board of Regeneron and has received research funding from Partner Therapeutics and travel funds from Roche/Genentech. Dr. Yarchoan has received research support from Bristol-Myers Squibb, Incyte and Genentech and honoraria from Genentech, Exelixis, Eisai, AstraZeneca, Replimune, and Hepion. Dr. Yarchoan is a co-founder of Adventris Pharmaceuticals and holds equity. Dr. Kelley has received research funding from Agios, Astra Zeneca, Bayer, BMS, Eli Lilly, EMD Serono, Exelixis, Genentech/Roche, Loxo Oncology, Merck, Novartis, Partner Therapeutics, QED, Relay Therapeutics, Surface Oncology, and Taiho, as well as consulting/advisory fees from Agios, Astra Zeneca, BMS, Exelixis, Ipsen, Merck, Compass, Exact Sciences, Kinnate, Regeneron, and Tyra Therapeutics. She has received travel support from: Astra Zeneca and Merck.

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Gordan, J.D., Keenan, B.P., Lim, H.C. et al. New Opportunities to Individualize Frontline Therapy in Advanced Stages of Hepatocellular Carcinoma. Drugs 83, 1091–1109 (2023). https://doi.org/10.1007/s40265-023-01907-3

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