ReviewTreatment options for EGFR mutant NSCLC with CNS involvement-Can patients BLOOM with the use of next generation EGFR TKIs?

- Cranial metastases are frequent sites of progression.
- Surgery, stereotactic radiosurgery and/or WBRT has been the cornerstone of therapy.
- Earlier EGFR TKIs have efficacy for CNS metastases.
- Earlier EGFR TKIs are limited by its ability to cross the BBB.
- Osimertinib and AZD3759, have very promising CNS activity.

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.