Intracranial Activity of Cabozantinib in MET Exon 14-Positive NSCLC with Brain Metastases

被引：72

作者：

Klempner, Samuel J. ^{[1
,2
]}

Borghei, Ali ^{[3
]}

Hakimian, Behrooz ^{[4
]}

Ali, Siraj M. ^{[5
]}

Ou, Sai-Hong Ignatius ^{[6
]}

机构：

[1] Angeles Clin & Res Inst, Los Angeles, CA USA

[2] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[3] Angeles Clin & Res Inst, Dept Radiol, Los Angeles, CA USA

[4] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA

[5] Fdn Med Inc, Cambridge, MA USA

[6] Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Dept Med,Div Hematol Oncol, Orange, CA 92668 USA

来源：

JOURNAL OF THORACIC ONCOLOGY | 2017年 / 12卷 / 01期

关键词：

MET exon 14; NSCLC; Crizotinib; Cabozantinib; Brain metastases; Comprehensive genomic profiling; CELL LUNG-CANCER; KINASE INHIBITOR; CRIZOTINIB; RESISTANCE; MUTATIONS; MODELS; POTENT;

D O I：

10.1016/j.jtho.2016.09.127

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

引用

页码：152 / 156

页数：5

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