August 2016 A 51-year-old female presents to her physician with symptoms of fatigue, intermittent chest pain, and lower back pain PMH: hypertension managed on a calcium channel blocker; osteoarthritis No history of smoking CT of the chest showed a 4.5-cm mass in the upper right lobe and enlarged hilar lymph nodes Bronchoscopy and transbronchial lung biopsy were performed: Pathology revealed a grade 2 adenocarcinoma, consistent with a lung primary tumor Molecular testing: FISH: positive forALKtranslocation NGS: negative forEGFR, ROS1, RET, BRAF, KRAS IHC: PD-L1 expression in 0% of cells Staging with PET/CT showed18F-FDG uptake in the lung mass, hilar nodes, and lumbar spine (L4/L5) Brain MRI, negative for intracranial metastases The patient was started on therapy with crizotinib Follow-up imaging at 3 and 6 months showed marked regression of the lung mass, nodal spread, and bone lesions June 2017 After 9 months on crizotinib, the patient reported worsening fatigue and back pain CT showed increased size of the pulmonary mass and bone lesions Brain MRI showed disseminated small lesions Crizotinib was discontinued and the patient was started on brigatinib