卡博替尼在 MET 外显子 14 阳性 NSCLC 伴脑转移患者中的颅内活性。
Intracranial Activity of Cabozantinib in MET Exon 14-Positive NSCLC with Brain Metastases.
机构信息
The Angeles Clinic and Research Institute, Los Angeles, California; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Department of Radiology, The Angeles Clinic and Research Institute, Los Angeles, California.
出版信息
J Thorac Oncol. 2017 Jan;12(1):152-156. doi: 10.1016/j.jtho.2016.09.127. Epub 2016 Sep 28.
INTRODUCTION
A significant portion of NSCLCs with MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping alterations are sensitive to small-molecule mesenchymal-epithelial transition tyrosine kinase inhibitors. However, the incidence and management of brain metastases in this molecular subset is unknown and represents an unmet clinical need.
METHODS
Hybrid capture-based comprehensive genomic profiling identified a patient with a MET exon 14 skipping alteration, and serial magnetic resonance imaging was utilized to follow intracranial disease during crizotinib and subsequent cabozantinib therapy.
RESULTS
Intracranial progression developed in the context of ongoing extracranial disease control during crizotinib therapy. Rapid intracranial response was observed after change to cabozantinib.
CONCLUSIONS
This report provides the first detailed description of brain metastases in MET exon 14-positive NSCLC and provides preliminary support for the intracranial activity of cabozantinib. Prospective study is warranted and needed to refine the management of intracranial disease in MET exon 14-positive NSCLC.
简介
具有 MET 原癌基因、受体酪氨酸激酶基因 (MET) 外显子 14 跳跃改变的 NSCLC 有相当一部分对小分子间质上皮转化酪氨酸激酶抑制剂敏感。然而，这一分子亚群中脑转移的发生率和管理尚不清楚，这是一个未满足的临床需求。
方法
基于杂交捕获的全面基因组分析确定了一名具有 MET 外显子 14 跳跃改变的患者，并利用磁共振成像（MRI）对克唑替尼和随后的卡博替尼治疗期间颅内疾病进行连续随访。
结果
在克唑替尼治疗期间，颅内疾病进展发生在外周疾病控制的情况下。改用卡博替尼后，颅内反应迅速。
结论
本报告首次详细描述了 MET 外显子 14 阳性 NSCLC 中的脑转移，并为卡博替尼的颅内活性提供了初步支持。需要进行前瞻性研究来完善 MET 外显子 14 阳性 NSCLC 中颅内疾病的管理。
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