a Department of Internal Medicine , National Taiwan University Hospital Hsin-Chu Branch , Hsinchu , Taiwan.
b Department of Oncology , National Taiwan University Hospital , Taipei , Taiwan.
Expert Rev Gastroenterol Hepatol. 2019 Jul;13(7):615-621. doi: 10.1080/17474124.2019.1621165. Epub 2019 May 27.
: Clinical trials in hepatocellular carcinoma (HCC) exhibit a high degree of heterogeneity. These heterogeneities may lead to unexpected results among clinical trials. : In this review, we address the heterogeneity noted in early phase HCC trials, trials involving transarterial chemoembolization, and advanced HCC trials. Furthermore, we discuss possible methods to attenuate the detrimental effects of heterogeneity when conducting clinical trials. : Clinical trials in HCC exhibit an inherently high degree of heterogeneity because of various reasons: tumor heterogeneity, different cirrhotic backgrounds, various etiologies of cirrhosis, and geographical differences in practice and expertise. Such heterogeneity may cause imbalance among the enrolled patient population, premature withdrawal from the clinical trial, and variable response to the treatment. In addition, methodological heterogeneity also exists in designing trial protocol and response evaluation. All these factors may eventually lead to conflicting results among clinical trials. Accounting for these heterogeneities is important to foster the success of future trials. In recent years, significant progress with molecular targeted agents and immune checkpoint inhibitors was made in advanced HCC. These new agents are also being tested in clinical trials involving earlier stage HCC and will also face the challenge of these issues.
肝细胞癌 (HCC) 的临床试验表现出高度的异质性。这些异质性可能导致临床试验中出现意外结果。
在这篇综述中，我们讨论了早期 HCC 试验、经动脉化疗栓塞试验和晚期 HCC 试验中观察到的异质性。此外，我们还讨论了在进行临床试验时减轻异质性不利影响的可能方法。
由于多种原因，HCC 的临床试验固有地存在高度异质性：肿瘤异质性、不同的肝硬化背景、肝硬化的各种病因以及实践和专业知识的地理差异。这种异质性可能导致入组患者人群的不平衡、过早退出临床试验以及对治疗的反应不同。此外，在设计试验方案和反应评估方面也存在方法学异质性。所有这些因素最终可能导致临床试验结果相互矛盾。考虑到这些异质性对于未来试验的成功非常重要。近年来，在晚期 HCC 中，分子靶向药物和免疫检查点抑制剂取得了重大进展。这些新药物也正在早期 HCC 的临床试验中进行测试，它们也将面临这些问题的挑战。
