New Systemic Therapies for Advanced Hepatocellular Carcinoma

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Since the approval of sorafenib for patients with advanced hepatocellular carcinoma (HCC) in 2007, many drugs have failed in the first and second-line setting. Fortunately, during the recent 2 years, between 2017 and 2018, four drugs (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were found to be effective and tolerable for patients with HCC as the first- or second-line therapy. Regorafenib, a multi-kinase inhibitor, has a similar structure to sorafenib, and was shown to improve the survival of patients who progressed after sorafenib treatment compared to the placebo control. According to the phase III trial of regorafenib, it became the first approved systemic therapy for patients with progression after sorafenib. Lenvatinib is also a tyrosine kinase inhibitor (TKI), and in a phase III trial comparing sorafenib and lenvatinib, the primary end-point of non-inferior survival was met. Based on the trial results, lenvatinb has become another systemic therapy for treatment-na?ve patients with advanced HCC. Cabozantinib is a dual inhibitor of Mesenchymal-Epithelial Transition factor/Vascular Endothelial Growth Factor Receptor2, and was shown to prolong the overall survival in patients who progressed after sorafenib compared to the placebo. Ramucirumab is a monoclonal antibody to inhibit a single target of VEGFR2. First, this drug failed to improve the survival of patients who progressed after sorafenib failure. On the other hand, it was effective in patients with baseline AFP ≥400 ng/mL, In a subsequent clinical trial that enrolled only patients with AFP ≥400 ng/mL, ramucirumab was also found to improve the overall survival compared to placebo. Thus, ramucirumab became the first biomarker-driven systemic treatment. Another category of drugs that are attracting considerable interest are immune checkpoint inhibitors, such as anti-programmed cell death protein (PD) 1 or anti-PD-ligand 1. This review provides a synopsis of new systemic therapies, including TKI, monoclonal antibody, and immune-oncology drugs.

Original languageEnglish
Pages (from-to)10-15
Number of pages6
JournalThe Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi
Volume73
Issue number1
DOIs
Publication statusPublished - 2019 Jan 25

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Hepatocellular Carcinoma
Survival
Pharmaceutical Preparations
Therapeutics
Placebos
Protein-Tyrosine Kinases
Programmed Cell Death 1 Receptor
Monoclonal Antibodies
Epithelial-Mesenchymal Transition
sorafenib
Vascular Endothelial Growth Factor A
Phosphotransferases
Biomarkers
Clinical Trials
Ligands
ramucirumab
lenvatinib
regorafenib

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "New Systemic Therapies for Advanced Hepatocellular Carcinoma",
abstract = "Since the approval of sorafenib for patients with advanced hepatocellular carcinoma (HCC) in 2007, many drugs have failed in the first and second-line setting. Fortunately, during the recent 2 years, between 2017 and 2018, four drugs (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were found to be effective and tolerable for patients with HCC as the first- or second-line therapy. Regorafenib, a multi-kinase inhibitor, has a similar structure to sorafenib, and was shown to improve the survival of patients who progressed after sorafenib treatment compared to the placebo control. According to the phase III trial of regorafenib, it became the first approved systemic therapy for patients with progression after sorafenib. Lenvatinib is also a tyrosine kinase inhibitor (TKI), and in a phase III trial comparing sorafenib and lenvatinib, the primary end-point of non-inferior survival was met. Based on the trial results, lenvatinb has become another systemic therapy for treatment-na?ve patients with advanced HCC. Cabozantinib is a dual inhibitor of Mesenchymal-Epithelial Transition factor/Vascular Endothelial Growth Factor Receptor2, and was shown to prolong the overall survival in patients who progressed after sorafenib compared to the placebo. Ramucirumab is a monoclonal antibody to inhibit a single target of VEGFR2. First, this drug failed to improve the survival of patients who progressed after sorafenib failure. On the other hand, it was effective in patients with baseline AFP ≥400 ng/mL, In a subsequent clinical trial that enrolled only patients with AFP ≥400 ng/mL, ramucirumab was also found to improve the overall survival compared to placebo. Thus, ramucirumab became the first biomarker-driven systemic treatment. Another category of drugs that are attracting considerable interest are immune checkpoint inhibitors, such as anti-programmed cell death protein (PD) 1 or anti-PD-ligand 1. This review provides a synopsis of new systemic therapies, including TKI, monoclonal antibody, and immune-oncology drugs.",
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New Systemic Therapies for Advanced Hepatocellular Carcinoma. / Kim, Do Young.

In: The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi, Vol. 73, No. 1, 25.01.2019, p. 10-15.

Research output: Contribution to journalReview article

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