Department of Health Sciences, University of Florence, viale Pieraccini, 6, 50139, Florence, Italy.
Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129, Trieste, Italy.
Invest New Drugs. 2019 Dec;37(6):1274-1288. doi: 10.1007/s10637-019-00760-0. Epub 2019 Mar 16.
The second line treatment of hepatocellular carcinoma (HCC) has recently become an exciting area of interest since new emerging options have demonstrated survival benefits versus placebo. Unfortunately, predictive biomarkers are unavailable for these treatments. Ramucirumab, a monoclonal antibody against VEGFR-2, has demonstrated overall survival superiority against placebo as a second line therapy for patients with AFP > 400 ng/ml in the recent REACH-2 trial. This review will provide the current updated knowledge regarding the HCC cancerogenesis and angiogenic VEGF/VEGFR-2 pathways and the clinical development of ramucirumab in advanced HCC. This study will also critically assess the gaps in a previous negative phase III trial that tested other potentially useful treatments and suggest ways to modernise clinical trials and personalise therapy for advanced HCC.
肝细胞癌 (HCC) 的二线治疗最近成为一个令人兴奋的研究领域，因为新出现的治疗方案显示出比安慰剂更优的生存获益。不幸的是，这些治疗方法缺乏预测生物标志物。雷莫芦单抗是一种针对 VEGFR-2 的单克隆抗体，在最近的 REACH-2 试验中，对于 AFP>400ng/ml 的 HCC 患者，二线治疗的总体生存优于安慰剂。本综述将提供关于 HCC 癌变和血管生成 VEGF/VEGFR-2 通路的最新知识，以及雷莫芦单抗在晚期 HCC 中的临床开发情况。本研究还将批判性地评估之前一项 III 期阴性试验中的空白点，该试验测试了其他可能有用的治疗方法，并提出了使晚期 HCC 的临床试验现代化和实现个体化治疗的方法。
