A 48-year-old female was a never-smoker and had a history of pulmonary tuberculosis cured by medication. The pulmonary nodule was found on chest X-ray, and NSCLC (adenocarcinoma) with brain and bone metastases was diagnosed in further evaluation in January 2017. She underwent gamma-knife surgery (GKS) for metastatic brain lesion and radiotherapy for pelvic and spinal bone metastases, followed by gefitinib because EGFR L858R mutation was identified. After 15 months, disease progression was noted, and pemetrexed plus cisplatin were administered as second-line therapy because there was no T790M mutation upon repeat biopsy. However, in August 2020, the patient complained of a headache, and spinal tap revealed increased intracranial pressure (IICP) and was positive for craniospinal fluid (CSF) cytology. To control IICP, a ventricle-peritoneal (VP) shunt was inserted. Given the newly developed LM and progression of extracranial disease, 80 mg of osimertinib once daily was started for LM; and bevacizumab, docetaxel, and carboplatin were administered for extracranial disease. Since then, the patient has continued combination therapy for 9.6 months without progression of LM or extracranial disease. The patient complained of general weakness of grade 1 without other adverse events. However, eventually, the patient died of pneumonia progressive to septic shock in January 2021. The brain magnetic resonance images (MRI) before and after osimertinib administration are presented in Fig. 1A.