1 Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic Rochester , Minnesota.
2 Division of Medical Oncology, Mayo Clinic Rochester , Minnesota.
Thyroid. 2017 Jul;27(7):923-927. doi: 10.1089/thy.2016.0627. Epub 2017 May 31.
Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only five months and <20% one-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding the use of lenvatinib in ATC. The aim of this study was to delineate clinical outcomes in a series of patients with advanced ATC in response to lenvatinib therapy.
A retrospective analysis was conducted involving all lenvatinib-treated Mayo Clinic ATC patients in 2015.
Of 28 distinct ATC patients seen in 2015, three (11%) with metastatic disease of ECOG performance status 2-3 were treated with lenvatinib. Two patients were male; age range at ATC diagnosis was 57-84 years. All three patients attained successful local control of their disease with surgery and/or combined chemoradiotherapy. Lenvatinib was offered as the second, third, or fourth line of therapy at the time of metastatic disease progression. Two patients incurred minor responses to therapy, with structural regression of distant metastatic tumor disease soon after starting lenvatinib treatment (at one to two months), while one patient achieved stable disease, but no Response Evaluation Criteria In Solid Tumors partial responses resulted. Overall survival after starting lenvatinib was two, six, and seven months. Fatigue and hypertension were prominent, and one patient developed pulmonary emboli while on lenvatinib.
This initial single-institution experience suggests that lenvatinib may have some disease-modifying activity in metastatic ATC that is otherwise refractory to cytotoxic chemotherapy. Unfortunately, observed benefits were transient, and toxicities were prominent. Clinical trials are required to ascertain better the utility of lenvatinib in the management of advanced ATC.
历史上，间变性甲状腺癌（ATC）的预后极差，中位生存期仅为 5 个月，1 年生存率<20%。目前，IVA 和 IVB 期疾病采用积极的初始治疗可改善预后，但远处转移（IVC 期）患者预后仍较差；迫切需要改善治疗方法。激酶抑制剂在晚期髓样和分化型甲状腺癌的治疗中已显示出良好的效果，但关于仑伐替尼在 ATC 中的应用数据有限。本研究旨在描述一系列晚期 ATC 患者接受仑伐替尼治疗的临床结局。
对 2015 年梅奥诊所接受仑伐替尼治疗的所有 ATC 患者进行回顾性分析。
2015 年共诊治 28 例明确的 ATC 患者，3 例（11%）转移性疾病 ECOG 表现状态为 2-3 的患者接受了仑伐替尼治疗。2 例为男性；ATC 诊断时年龄范围为 57-84 岁。所有 3 例患者均通过手术和/或联合放化疗成功控制了局部疾病。仑伐替尼是在转移性疾病进展时作为二线、三线或四线治疗药物提供的。2 例患者对治疗有轻微反应，在开始仑伐替尼治疗后 1-2 个月，远处转移性肿瘤疾病的结构消退，1 例患者病情稳定，但未达到实体瘤反应评价标准的部分缓解。开始仑伐替尼治疗后总生存期分别为 2、6 和 7 个月。乏力和高血压较为突出，1 例患者在仑伐替尼治疗期间发生肺栓塞。
本初步单中心经验表明，仑伐替尼可能对其他细胞毒性化疗无效的转移性 ATC 具有一定的疾病改善作用。遗憾的是，观察到的益处是短暂的，且毒性明显。需要进行临床试验以更好地确定仑伐替尼在晚期 ATC 治疗中的应用。
