With the use of EGFR TKIs, patient survival is now prolonged and as a 
consequence, a higher chance of development of CNS metastases has been observed 
during the course of the disease. CNS metastases remains a therapeutically 
challenging subset of patient to treat owing to the blood-brain barrier (BBB). 
Prior to routine EGFR mutation testing, surgical resection, stereotactic 
radiosurgery and/or whole brain radiation therapy (WBRT) were the main treatment 
options whereas treatment options for patients with leptomeningeal metastases 
(LM) included intra-thecal chemotherapy, WBRT, and ventriculo-peritoneal 
shunting. Unfortunately outcome for both BM and LM remains poor with median 
survival between 3 and 6 months. Systemic treatment with EGFR TKIs had been 
effective in the treatment of intracranial metastases but efficacy of early 
generation TKIs were hampered by its limited BBB penetration. The next 
generation EGFR TKIs osimertinib and AZD3759 have improved BBB penetration and 
the BLOOM study of osimertinib and AZD3759 has reported highly promising 
intracranial efficacy and may herald a new frontier to treat this 
therapeutically challenging subset of advanced EGFR mutant patients.