Best Jan, Schotten Clemens, Lohmann Gregor, Gerken Guido, Dechêne Alexander
a Department of Gastroenterology and Hepatology , University Hospital Essen , Essen , Germany.
b Laboratory of Lymphocyte Signaling and Oncoproteome, Department of Internal Medicine I , Center for Integrated Oncology (CIO) Köln-Bonn, University of Cologne , Cologne , Germany.
Expert Opin Pharmacother. 2017 May;18(7):727-733. doi: 10.1080/14656566.2017.1316376. Epub 2017 Apr 17.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with a poor prognosis due to late diagnosis in the majority of cases. Physicians are frequently confronted with patients who are not eligible for curative or locoregional treatments any more. In this scenario, the multi-tyrosine kinase inhibitor sorafenib remains the only systemic first-line treatment option providing modest survival benefit compared to placebo with significant but for most patients acceptable adverse effects. Areas covered: Tivantinib was the first antiproliferative agent to be been applied in a phase III trial based on receptor overexpression analyses after disease progression on sorafenib. While phase I and II trials with tivantinib in second line showed encouraging results, a recent press release announced that the METIV-HCC phase III study of tivantinib in HCC did not meet its primary endpoint of improving overall survival. Expert commentary: Evidence for antiangiogenetic therapy inducing tumor hypoxia leading to overexpression of proliferative genes, including cMET, underlines the potential of tivantinib as second-line treatment. However, as the mechanism of action of tivantinib through cMET inhibition has recently been questioned by several groups, identification of alternative proliferative markers or targets is mandatory.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一，由于大多数病例诊断较晚，预后较差。医生经常会遇到不再适合进行根治性或局部区域治疗的患者。在这种情况下，多酪氨酸激酶抑制剂索拉非尼仍然是唯一的一线全身治疗选择，与安慰剂相比，它能提供适度的生存益处，同时伴有显著但大多数患者可接受的不良反应。涵盖领域：替万替尼是首个基于索拉非尼疾病进展后受体过表达分析而应用于III期试验的抗增殖药物。虽然替万替尼二线治疗的I期和II期试验显示出令人鼓舞的结果，但最近的一份新闻稿宣布，替万替尼治疗HCC的METIV-HCC III期研究未达到改善总生存期的主要终点。专家评论：抗血管生成治疗诱导肿瘤缺氧导致包括cMET在内的增殖基因过表达的证据，突显了替万替尼作为二线治疗的潜力。然而，由于替万替尼通过抑制cMET的作用机制最近受到几个研究小组的质疑，因此必须确定替代的增殖标志物或靶点。
