Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2021 Feb 15;27(4):928-932. doi: 10.1158/1078-0432.CCR-20-2771. Epub 2020 Sep 23.
The FDA-approved entrectinib on August 15, 2019, for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase () gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. Approval was based on demonstration of a durable overall response rate of 57% (95% confidence interval: 43-71), including a complete response rate of 7%, among 54 entrectinib-treated patients with 10 different tumor types harboring an fusion enrolled in one of three single-arm clinical trials. The durations of response ranged from 2.8 months to 26.0+ months; 68% of responses lasted ≥ 6 months. The most serious toxicities of entrectinib are congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders. Adverse reactions were manageable through dose interruptions (46%), dose reductions (29%), or discontinuation of entrectinib (9%). This is the third approval of a cancer drug for treatment of a tissue agnostic, biomarker-defined cancer.
美国食品药品监督管理局（FDA）于 2019 年 8 月 15 日批准恩曲替尼用于治疗成人和 12 岁及以上患有神经酪氨酸受体激酶（）基因融合而无已知获得性耐药突变的、无法手术切除的局部晚期或转移性实体瘤，或手术切除可能导致严重发病率的患者，以及在接受治疗后进展或没有满意的替代治疗的患者。批准基于在三个单臂临床试验之一中入组的 10 种不同肿瘤类型的 54 名携带 融合的恩曲替尼治疗患者中，有 57%（95%置信区间：43-71）的患者持久缓解，包括 7%的完全缓解率。反应持续时间从 2.8 个月到 26.0+个月不等；68%的缓解持续时间≥6 个月。恩曲替尼最严重的毒性是充血性心力衰竭、中枢神经系统效应、骨骼骨折、肝毒性、高尿酸血症、QT 间期延长和视力障碍。通过中断剂量（46%）、减少剂量（29%）或停止使用恩曲替尼（9%）可以控制不良反应。这是批准的第三款针对组织不可知、生物标志物定义的癌症的癌症药物。
