Zhang Bingnan, Finn Richard S
Division of Hematology Oncology Geffen School of Medicine at UCLA, Los Angeles, Calif., USA.
Liver Cancer. 2016 Jul;5(3):221-32. doi: 10.1159/000367763. Epub 2016 May 10.
Since the approval of sorafenib there have been numerous failures of new agents in Phase III studies for treatment of advanced hepatocellular carcinoma (HCC). These studies have generally ignored the molecular heterogeneity of HCC and they have not enrolled patients based on predictive markers of response. The development of molecular targeted therapeutics in HCC needs to model the approach that has been taken with great success in other solid tumors, to decrease the likelihood of failure in future studies.
Here we review the paradigm taken with novel targeted agents in other solid tumors and highlight ongoing studies in HCC that are incorporating biomarkers in clinical development.
With the appreciation of the molecular diversity of HCC, clinical development of new agents in HCC will need to be targeted towards those patients who are most likely to benefit. This strategy, based on biomarkers for patient selection, is more likely to yield positive results and mitigate the risk of continued negative Phase III studies.
自索拉非尼获批以来，在晚期肝细胞癌（HCC）的III期治疗研究中，众多新型药物均告失败。这些研究通常忽视了HCC的分子异质性，且未根据反应预测标志物纳入患者。HCC分子靶向治疗的发展需要借鉴在其他实体瘤中取得巨大成功的方法，以降低未来研究失败的可能性。
在此，我们回顾了在其他实体瘤中使用新型靶向药物的模式，并强调了HCC中正在进行的将生物标志物纳入临床开发的研究。
随着对HCC分子多样性的认识，HCC新型药物的临床开发将需要针对最可能受益的患者。这种基于生物标志物进行患者选择的策略更有可能产生积极结果，并降低III期研究持续失败的风险。
