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Systemic Treatment of Advanced Unresectable Hepatocellular Carcinoma after First-Line Therapy: Expert Recommendations from Hong Kong, Singapore, and Taiwan
Thomas Yau 1 , David Tai 2 , Stephen Lam Chan 3 , Yi-Hsiang Huang 4 5 , Su Pin Choo 6 , Chiun Hsu 7 , Tan To Cheung 8 , Shi-Ming Lin 9 , Wei Peng Yong 10 , Joycelyn Lee 2 , Thomas Leung 11 , Tracy Shum 12 , Cynthia S Y Yeung 13 , Anna Yin-Ping Tai 14 , Ada Lai Yau Law 15 , Ann-Lii Cheng 16 17 , Li-Tzong Chen 18 19
Affiliations
Affiliations
1
Department of Medicine, The University of Hong Kong, Hong Kong, China.
2
Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
3
Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China.
4
Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
5
Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
6
Curie Oncology, Singapore, Singapore.
7
Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
8
Department of Surgery, The University of Hong Kong, Hong Kong, China.
9
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkuo, Taiwan.
10
Department of Haematology-Oncology, National University of Singapore, Singapore, Singapore.
11
Department of Medical Oncology, Hong Kong Sanatorium & Hospital, Hong Kong, China.
12
Department of Oncology, Princess Margaret Hospital, Hong Kong, China.
13
Union Hospital, Hong Kong, China.
14
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China.
15
Chiron Medical, Hong Kong, China.
16
Department of Internal Medicine and Oncology, National Taiwan University Hospital, Taipei, Taiwan.
17
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
18
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
19
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
PMID: 36158587 PMCID: PMC9485972 DOI: 10.1159/000525582
Abstract
Background: Asia has a high burden of hepatocellular carcinoma (HCC) due to the high rates of chronic hepatitis B infection and accounts for 70% of HCC cases globally. In the past 20 years, the systemic treatment landscape of advanced HCC has evolved substantially - from tyrosine kinase inhibitors to immune-oncology agents plus anti-vascular endothelial growth factor agents. The appropriate sequence of therapies has become critical in optimizing patient outcomes given the increase in systemic therapeutic options. This article evaluates the evidence and provides expert recommendations for the use of systemic therapies after first-line treatment in patients with advanced HCC.
Summary: Based on three virtual meetings held in early 2021, a team of 17 experts comprising oncologists, a hepatologist, and a hepatobiliary surgeon from Hong Kong, Singapore, and Taiwan reviewed available data about systemic treatments for HCC after first line and formulated 28 statements. These statements aimed to provide expert guidance on selecting first and subsequent lines of therapies as well as recommending therapies in special circumstances, such as poor liver function, posttransplantation, recent gastrointestinal bleeding, or autoimmune diseases. Data supporting the statements were drawn from clinical trials and real-world studies. The 28 statements were then evaluated anonymously using a 5-point Likert scale, and 24 reached consensus, predefined as achieving 75% agreement. Statements generated covered the selection of first-line systemic therapy, considerations and goals of second-line systemic therapies, treatment selection following first-line therapy, and treatment recommendations following first-line tyrosine kinase inhibitors, immune-oncology monotherapy, or immune-oncology combination therapy. The authors also shared expert opinion on the use of second-line systemic therapy in patients with liver dysfunction, liver transplantation, and recent gastrointestinal or autoimmune disease.
Key messages: These expert statements summarize the latest data and expert opinion on selecting systemic treatment following first-line therapy in patients with unresectable advanced or metastatic HCC.
Keywords: Hepatocellular carcinoma; Liver cancer; Systemic treatment.
Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.
Conflict of interest statement
Dr. Chan has received consulting fees from AstraZeneca, Merck Sharp & Dohme, Eisai, and Ipsen and research funding from Bayer, Eisai, Ipsen, Sirtex, and Merck Sharp & Dohme. Dr. Chan is also an Editorial Board Member of Liver Cancer. Dr. Chen has received grants from GlaxoSmithKline, Merck Serono, OBI Pharma, Pfizer, Polaris, Ministry of Science and Technology, and the Ministry of Health and Welfare; personal fees from Bristol Myers Squibb, Eli Lilly, Five Prime, Merck Sharp & Dohme, Merrimack Pharmaceuticals, Ono Pharmaceutical, PharmaEngine, and Shire; grants and nonfinancial support from Celgene; and grants, personal fees, and nonfinancial support from Novartis, Syncore, and TTY Biopharm. Dr. Cheng has received travel support from Bayer Yakuhin, Ltd., Eisai, Roche/Genentech, Chugai Pharmaceutical, and IQVIA; honoraria for speakers bureau from Bayer Yakuhin, Ltd., Novartis, Eisai, Ono Pharmaceutical, and Amgen Taiwan; and consulting fee from AstraZeneca, Bristol Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, IPSEN Innovation, Bayer Healthcare, Merck Sharp & Dohme, Roche/Genentech, BeiGene, F. Hoffmann-La Roche, and IQVIA. Dr. Cheng is an Associate Editor of Liver Cancer. Dr. Choo owns stock/shares of Bristol Myers Squibb and has received honoraria and consulting fee from Bristol Myers Squibb, Bayer, Roche, AstraZeneca, Merck Sharp & Dohme, and Ipsen; she has also received honoraria from Eisai. Dr. Hsu has received honoraria from AstraZeneca, Bayer, Bristol Myers Squibb/Ono Pharmaceuticals, Eisai, Ipsen, Merck Sharpe & Dohme, and Roche; and grants or funds from Bristol Myers Squibb/Ono Pharmaceuticals, Roche, and Ipsen. Professor Huang has been an advisory council or committee member and received honoraria from AbbVie, Gilead Sciences, Bristol Myers Squibb, Ono Pharmaceuticals, Eisai, Eli Lilly, Ipsen, Merck Sharp & Dohme, and Roche; and received grants or funds from Gilead Sciences and Bristol Myers Squibb. Dr. Lee has received honoraria from Bristol Myers Squibb, Ipsen, and Bayer; and grants or funds from Bayer. Dr. DWM Tai has been an advisory council or committee member, received honoraria and consulting fees from Novartis, Sirtex, Merck Sharpe & Dohme, Celgene, Eisai, and Bristol Myers Squibb; he has also received grants or funds from Novartis, Bristol Myers Squibb, and Sirtex. Dr. Yau has been an advisory council or committee member and received honoraria from Bristol Myers Squibb, Merck Sharpe & Dohme, Exelixis, Ipsen, Eisai, AstraZeneca, Bayer, Novartis, EMD Sereon, AbbVie, Pfizer, Eli Lilly, Sirtex, Sillajen, Taiho, OrigiMed, New B Innovation, Sirtex, and H3 Biomedicine. Dr. Yong has received honoraria from Amgen, Genentech, Bayer, Merck Sharpe & Dohme, Bristol Myers Squibb, Ipsen, Novartis, AstraZeneca, Eli Lilly, and Taiho. Drs Cheung, Law, Leung, Lin, Shum, A.Y.P. Tai, and Yeung have no potential conflict of interest to declare.
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