Novel systemic therapy for hepatocellular carcinoma
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REVIEW ARTICLE
Novel systemic therapy for hepatocellular carcinoma Yawen Dong1 · Tsung‑Hao Liu2,3 · Thomas Yau1 · Chiun Hsu2,3 Received: 1 April 2020 / Accepted: 1 July 2020 © Asian Pacific Association for the Study of the Liver 2020
Abstract Systemic therapy for hepatocellular carcinoma (HCC) used to be limited to patients with advanced diseases and multi-kinase inhibitors targeting tumor angiogenesis the major approach of developing new treatment options. In the past 3 years, new data from trials of both molecular targeted therapy and immune checkpoint inhibitors (ICI) provided many new options of first- and second-line treatment for advanced HCC. Most notably, combination of ICI targeting the program cell death-1 (PD-1) pathway with other novel agents or conventional anti-cancer therapy may further improve treatment efficacy in different clinical settings. In this paper updated data of clinical trials of systemic therapy in the first- and second-line settings for advanced HCC were reviewed and the following issues were discussed: (1) lessons of trial design learned from positive and negative trials; (2) the balance between efficacy and safety in clinical practice; and (3) impact on future multi-disciplinary management of HCC. Keywords Accelerated approval · Adverse events · Anti-angiogenesis · Combination therapy · Cytotoxic T-lymphocyteassociated protein-4 (CTLA-4) · Immune checkpoint inhibitor · Molecular targeted therapy · Multi-disciplinary management · Program cell death-1 (PD-1) · Randomized control trials
Systemic therapy for advanced hepatocellular carcinoma (HCC): realization of multi‑disciplinary management The history of development of systemic therapy for advanced HCC has taught us valuable lessons on how to improve trial design in recent years [1]. Results of early trials of systemic therapy were disappointing because most patients enrolled into these trials had impaired liver functional reserves and poor tolerance caused by the underlying liver cirrhosis, injury from prior loco-regional therapy,
Yawen Dong and Tsung-Hao Liu contributed equally to this work. * Thomas Yau [email protected] * Chiun Hsu [email protected] 1
Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
2
Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
3
Department of Oncology, National Taiwan University Hospital, 7 Chung‑Shan South Road, Taipei 10002, Taiwan
and the huge tumor burden. Therefore, most recent trials recruited subjects with Child A liver function and limited tumor burden in the liver. The exploration of new treatment options was largely limited to multi-kinase inhibitors targeting tumor angiogenesis reflected the difficulty of identifying driver mutations and designing specific agents for HCC [2]. In the past 3 years, new data from trials of both molecular targeted therapy and immune checkpoint inhibitors (ICI) provided many new options of first- and second-line treatment for advanced HCC (Table 1, Fig. 1)
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