Targeted agents for second-line treatment of advanced hepatocellular carcinoma |
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Authors: | Nicola Personeni Tiziana Pressiani Silvia Bozzarelli Lorenza Rimassa |
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Institution: | Nicola Personeni, Tiziana Pressiani, Silvia Bozzarelli, Lorenza Rimassa, Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milan, ItalyNicola Personeni, Lorenza Rimassa, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy |
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Abstract: | Over the past ten years, sorafenib, a multikinase inhibitor, has been the standard of care for patients with unresectable hepatocellular carcinoma (HCC) and well-preserved liver function. Recently, lenvatinib, a different multikinase inhibitor, was shown to be non-inferior to sorafenib, in terms of survival, while all other agents previously tested failed to prove non-inferiority (or superiority) when compared to sorafenib. Similarly, in the second-line setting, most investigational drugs failed to provide better survival outcomes than placebo. However, in the last 2 years three positive phase III trials have been published in this setting. The RESORCE trial, a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib, showed better outcomes with regorafenib compared to placebo. More recently, the phase III CELESTIAL trial demonstrated the superiority of cabozantinib, a multikinase inhibitor targeting vascular endothelial growth factor receptor, MET, and AXL, vs placebo in the second- and third-line setting in patients progressing on or intolerant to sorafenib. The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels. Overall, the adverse events reported in these trials were in line with the known safety profiles of the tested agents. After nearly a decade of a certain degree of stagnation, we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC. |
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Keywords: | Hepatocellular carcinoma Advanced-metastatic Second-line Third-line Regorafenib Cabozantinib Ramucirumab Angiogenesis Multikinase inhibitor MET AXL Vascular endothelial growth factor receptor 2 |
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| 点击此处可从《World journal of gastrointestinal oncology》浏览原始摘要信息 |
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