Samuel J Klempner1, Ali Borghei2, Behrooz Hakimian3, Siraj M Ali4, Sai-Hong Ignatius Ou5. 1. The Angeles Clinic and Research Institute, Los Angeles, California; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: sklempner@theangelesclinic.org. 2. Department of Radiology, The Angeles Clinic and Research Institute, Los Angeles, California. 3. Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California. 4. Foundation Medicine, Inc., Cambridge, Massachusetts. 5. Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, California.
Abstract
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.
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.