BCLC group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Universitat de Barcelona, Barcelona, Spain.
Nat Rev Gastroenterol Hepatol. 2019 Oct;16(10):617-630. doi: 10.1038/s41575-019-0179-x. Epub 2019 Aug 1.
Systemic treatment for hepatocellular carcinoma (HCC) has been boosted by the incorporation of new agents after many negative phase III trials in the decade since the approval of sorafenib. Sorafenib introduced the concept that targeting specific hallmarks of hepatocarcinogenesis could modify the dismal prognosis of this disease, with the drug remaining a cornerstone in the upfront therapy for advanced HCC. The design of clinical trials in this malignancy is complicated by important obstacles related to patient selection, prognostic assessment and the need for endpoints that correlate with improvement in survival outcomes. In addition, the currently used criteria to determine treatment response or progression might prevent physicians from making appropriate clinical judgements and interpreting evidence arising from trials. In this Review, we discuss the advances in systemic therapy for HCC and critically review trial designs in HCC. Although novel therapies, such as new targeted agents and immunotherapies, are being rapidly incorporated, it is paramount to design future clinical trials based on the lessons learned from past failures and successes.
索拉非尼获批上市后的十年间，多项 III 期临床试验结果均为阴性，此后，新型药物的问世推动了肝细胞癌（HCC）的系统治疗。索拉非尼开创了这样一种理念，即针对肝癌发生的特定特征进行靶向治疗可能会改善这种疾病的不良预后，该药物仍然是晚期 HCC 一线治疗的基石。由于与患者选择、预后评估以及需要与生存结果改善相关的终点相关的重要障碍，该肿瘤的临床试验设计较为复杂。此外，目前用于确定治疗反应或进展的标准可能会阻止医生做出适当的临床判断并解释来自试验的证据。在这篇综述中，我们讨论了 HCC 系统治疗的进展，并批判性地回顾了 HCC 的临床试验设计。虽然新型疗法，如新型靶向药物和免疫疗法，正在迅速被纳入治疗方案，但根据过去的成败经验来设计未来的临床试验至关重要。
