Radiotherapy in brain metastases from EGFR-mutated non-small cell lung cancer

Epidermal growth factor receptor (EGFR) mutations are present in 20-40% of non-small cell lung cancers (NSCLCs). Brain metastasis (BM) is more common in EGFR-mutated NSCLC (25-45%) compared to EGFR wild-type (15-30%). First and second-generation tyrosine kinase inhibitors (TKIs), such as erlotinib and afatinib have proven to be superior to chemotherapy in the front-line treatment of EGFR-mutated NSCLC. Osimertinib, a third-generation EGFR TKI, has demonstrated better blood brain barrier (BBB) penetration, higher rate of intracranial response (66% vs. 43%) and a lower rate of CNS progression when compared to first generation EGFR TKI. Evidence on upfront radiation vs. upfront osimertinib is limited, but rapidly evolving and being tested in ongoing comparative trials. Stereotactic radiation (SRS) is very effective in the control of BMs and has been increasingly used and consequently replacing resection of BMs. SRS also has been increasingly used in the treatment of multiple BMs. Considering the effectiveness of targeted agents such as third generation EGFR inhibitors clinicians now are more frequently faced with the decision, if systemic therapy is safe and effective enough to withhold SRS. Third generation EGFR inhibitors also have fewer adverse events as previous generations. This review discusses the current literature available for management of BM in EGFR-mutated NSCLC.