LAUSR

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.