Relapsed ALK-Rearranged NSCLC

Case: A 53-Year-Old Woman WithALK-Rearranged NSCLC

• A 53-year-old woman presented with dyspnea, persistent cough with bloody sputum, and intermittent pain in right side of her chest
• Relevant PMH:
  • Nonsmoker, had childhood exposure to second-hand smoke
  • No history or presence of pneumonia or bronchitis
  • No history of diabetes, cardiovascular disease, or renal disease
• PE: lungs, clear; no palpable masses or visible lesions; patient is of average height and weight, appears physically fit
• Diagnostic workup:
  • Chest X-Ray: revealed multiple small solid lesions in right lung
  • CT with contrast chest/abdomen/pelvis: several hyperattenuated tumors in right lung
  • Biopsy confirmed lung adenocarcinoma
  • Molecular testing:
    • Genetic testing;EGFR, BRAF, RET,KRAS, HER2wild-type,ROS1FISH
    • IHC;ALK-rearrangement
    • PD-L1 TPS; 20%
  • Brain MRI: revealed extensive CNS involvement
• Treatment:
  • Started on alectinib; achieved partial response
  • Developed fatigue, grade 1 constipation, and nausea; continued treatment
  • Imaging at 12 months showed disease progression
  • Tumor testing of a lung lesions demonstrated MET FISH+
• She was started on crizotinib
  • Imaging at 3 and 6 months showed a partial response
  • Developed grade 2 diarrhea and visual disturbance; continued treatment
  • Imaging at 10 months showed progression in the CNS lesions and the lung
  • Repeat biopsy of the lung lesions and genotyping showed ALK L1196M mutation
• She was started on brigatinib at 90 mg once daily; she tolerated therapy well and after 1 week, dose was increased to 180 mg once daily
  • Achieved partial response, including in CNS metastases
  • Had fatigue, but was able to resume some exercise
  • Remains on treatment 16 months later