维莫非尼在BRAF（V600E）阳性甲状腺乳头状癌患者中的疗效与耐受性：MD安德森癌症中心的非适应证用药经验
Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience.
作者信息
Dadu Ramona, Shah Komal, Busaidy Naifa L, Waguespack Steven G, Habra Mouhammad A, Ying Anita K, Hu Mimi I, Bassett Roland, Jimenez Camilo, Sherman Steven I, Cabanillas Maria E
机构信息
Departments of Endocrine Neoplasia and Hormonal Disorders (R.D., N.L.B., S.G.W., M.A.H., A.K.Y., M.I.H., C.J., S.I.S., M.E.C.), Diagnostic Radiology (K.S.), and Biostatistics (R.B.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
出版信息
J Clin Endocrinol Metab. 2015 Jan;100(1):E77-81. doi: 10.1210/jc.2014-2246.
CONTEXT
Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.
OBJECTIVE
To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.
DESIGN
A retrospective review at MD Anderson Cancer Center.
METHODS
The best responses were evaluated using RECIST v1.1. A single radiologist reviewed all images. Adverse events (AEs) were evaluated using CTCAE v.4.0.
RESULTS
We identified 17 patients with advanced PTC harboring the BRAF(V600E) mutation who were treated with vemurafenib outside of a clinical trial. Median age at diagnosis was 63 years, and 53% were male. At vemurafenib start, 3 (18%) patients had disease confined to the neck, and 14 (72%) had distant metastases. Tyrosine kinase inhibitors had been previously administered to 4 (24%) patients. Two (12%) patients discontinued vemurafenib because of AEs before restaging. Best response: partial response (PR) in 7/15 (47%) and stable disease (SD) in 8/15(53%) patients. The rate of durable response (PR plus SD ≥ 6 months) was 67%. Median time to treatment failure was 13 months. There was no association between change in thyroglobulin and tumor size. Drug discontinuation, drug interruptions, and dose reductions were needed in 5 (29%), 13 (76%), and 10 (59%) patients, respectively. Most common AEs were fatigue (71%), weight loss (71%), anorexia (65%), arthralgias (59%), hair loss (59%), rash (59%), hand-foot syndrome (53%), calluses (47%), diarrhea (47%), fever (41%), dry mouth (35%), nausea (35%), and verrucous keratosis (35%). Grade ≥ 3 AEs were present in 8 (47%) patients.
CONCLUSIONS
Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation. Our results are similar to those reported in a phase II clinical trial and support the potential role of vemurafenib in this patient population.
背景
维莫非尼是一种选择性BRAF抑制剂，在携带BRAF（V600E）突变的甲状腺乳头状癌（PTC）患者中似乎具有良好的临床活性。
目的
确定维莫非尼在临床试验之外使用时的疗效和安全性。
设计
在MD安德森癌症中心进行的一项回顾性研究。
方法
使用RECIST v1.1评估最佳反应。由一名放射科医生审查所有图像。使用CTCAE v.4.0评估不良事件（AE）。
结果
我们确定了17例携带BRAF（V600E）突变的晚期PTC患者，他们在临床试验之外接受了维莫非尼治疗。诊断时的中位年龄为63岁，53%为男性。开始使用维莫非尼时，3例（18%）患者疾病局限于颈部，14例（72%）有远处转移。4例（24%）患者先前接受过酪氨酸激酶抑制剂治疗。2例（12%）患者在重新分期前因AE停用维莫非尼。最佳反应：7/15例（47%）患者为部分缓解（PR），8/15例（53%）患者为疾病稳定（SD）。持久反应率（PR加SD≥6个月）为67%。治疗失败的中位时间为13个月。甲状腺球蛋白变化与肿瘤大小之间无关联。分别有5例（29%）、13例（76%）和10例（59%）患者需要停药、中断用药和减量。最常见的AE为疲劳（71%）、体重减轻（71%）、厌食（65%）、关节痛（59%）、脱发（59%）、皮疹（59%）、手足综合征（53%）、胼胝（47%）、腹泻（47%）、发热（41%）、口干（35%）、恶心（35%）和疣状角化病（35%）。8例（47%）患者出现≥3级AE。
结论
维莫非尼对于携带BRAF（V600E）突变的晚期PTC患者是一种潜在有效的且耐受性良好的治疗策略。我们的结果与一项II期临床试验报告的结果相似，并支持维莫非尼在该患者群体中的潜在作用。
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