New Systemic Therapies for Advanced Hepatocellular Carcinoma
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 foun...
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| Format: | Article |
| Language: | English |
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Jin Publishing & Printing Co.
2019-01-01
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| Series: | The Korean Journal of Gastroenterology |
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| Online Access: | http://www.kjg.or.kr/journal/view.html?doi=10.4166/kjg.2019.73.1.10 |
| _version_ | 1818081627840970752 |
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| author | Do Young Kim |
| author_facet | Do Young Kim |
| author_sort | Do Young Kim |
| collection | DOAJ |
| description | 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-naïve 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. |
| first_indexed | 2024-12-10T19:09:13Z |
| format | Article |
| id | doaj.art-a5b958cd1936430aa1528122962e793c |
| institution | Directory Open Access Journal |
| issn | 1598-9992 |
| language | English |
| last_indexed | 2024-12-10T19:09:13Z |
| publishDate | 2019-01-01 |
| publisher | Jin Publishing & Printing Co. |
| record_format | Article |
| series | The Korean Journal of Gastroenterology |
| spelling | doaj.art-a5b958cd1936430aa1528122962e793c2022-12-22T01:36:49ZengJin Publishing & Printing Co.The Korean Journal of Gastroenterology1598-99922019-01-01731101510.4166/kjg.2019.73.1.10kjg.2019.73.1.10New Systemic Therapies for Advanced Hepatocellular CarcinomaDo Young Kim0Department of Internal Medicine, Yonsei University College of Medicine, Seoul, KoreaSince 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-naïve 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.http://www.kjg.or.kr/journal/view.html?doi=10.4166/kjg.2019.73.1.10CarcinomahepatocellularTherapeuticsOncology |
| spellingShingle | Do Young Kim New Systemic Therapies for Advanced Hepatocellular Carcinoma The Korean Journal of Gastroenterology Carcinoma hepatocellular Therapeutics Oncology |
| title | New Systemic Therapies for Advanced Hepatocellular Carcinoma |
| title_full | New Systemic Therapies for Advanced Hepatocellular Carcinoma |
| title_fullStr | New Systemic Therapies for Advanced Hepatocellular Carcinoma |
| title_full_unstemmed | New Systemic Therapies for Advanced Hepatocellular Carcinoma |
| title_short | New Systemic Therapies for Advanced Hepatocellular Carcinoma |
| title_sort | new systemic therapies for advanced hepatocellular carcinoma |
| topic | Carcinoma hepatocellular Therapeutics Oncology |
| url | http://www.kjg.or.kr/journal/view.html?doi=10.4166/kjg.2019.73.1.10 |
| work_keys_str_mv | AT doyoungkim newsystemictherapiesforadvancedhepatocellularcarcinoma |