In this regard, the third-generation TKI osimertinib has shown a higher penetration through the BBB (CSF level 7.51 and 25.2 nmol/L when administered at 160 mg/day and 300 mg bid, respectively) and now is considered the first-line therapy in LM from EGFR-mutated NSCLC based on the results of several studies [115,116,117,118,119,120,121,122,123], regardless of T790 mutation status [121] (Table 4). Here, EGFR is linked to non-small cell lung carcinoma.