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



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.



Intracranial progression developed in the context of ongoing extracranial disease control during crizotinib therapy. Rapid intracranial response was observed after change to cabozantinib.



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.
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.
Samuel J
SJ
Klempner
Department of Radiology, The Angeles Clinic and Research Institute, Los Angeles, California.
Ali
A
Borghei
Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
Behrooz
B
Hakimian
Foundation Medicine, Inc., Cambridge, Massachusetts.
Siraj M
SM
Ali
Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, California.
Sai-Hong Ignatius
SI
Ou
D000368:Aged; D000813:Anilides / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D011725:Pyridines / Q000627:therapeutic use*
D000813:Anilides; D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011725:Pyridines; C558660:cabozantinib; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Brain metastases; Cabozantinib; Comprehensive genomic profiling; Crizotinib; MET exon 14; NSCLC