AACR 2023 -- Clinically lung cancer often metastasizes to the brain, significantly reducing life expectancy. Many patients with non-small cell lung cancer (NSCLC) already have brain metastasis when they are first diagnosed. Currently there are no targeted therapies specific for brain metastases, and the blood-brain barrier can pose a physiologic impediment to many cytotoxic drugs and antibody-based therapies. Xenograft models for metastatic brain disease via a direct intracranial implant coupled with a subcutaneous "primary" tumor effectively allow evaluation of the response to treatment at both locations. NCI-H1975-Luc and PC-9-Luc-mCh-puro are both human non-small cell lung carcinoma cell lines that harbor unique mutational EGFR T790M status. Osimertinib, an approved first-line treatment for EGFR+ NSCLC patients, was investigated in these tumor models.