Upfront radiation versus EGFR-TKI: which is the best approach for EGFR-mutated NSCLC patients with brain metastasis?

In The Journal of Clinical Oncology, William J. Magnuson (1) and colleagues have recently reported the results of a multicenter retrospective analysis comparing the impact of three different treatment strategies on survival outcomes of 351 patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) and brain metastases (BM). Treatment options included stereotactic radiosurgery (SRS) followed by EGFR-TKI (n=100), whole-brain radiotherapy (WBRT) followed by EGFR-TKI (n=120), or EGFR-TKI followed by SRS or WBRT at the time of intracranial progression (n=131). Results showed a significantly longer median overall survival (OS) in patients who received upfront SRS (46 months) as compared to WBRT (30 months) or upfront TKI (25 months) (P<0.001), suggesting SRS followed by EGFR-TKI as the best treatment approach for these patients. The significant survival improvement was independent from significant prognostic covariables such as age, ECOG performance status, number of BM, EGFR mutation, and extracranial metastases, which were included in the multivariable analysis. The upfront use of radiotherapy resulted also in a significantly longer median time to intracranial progression (23 vs. 18 months; P=0.025) and 2-year OS rate (78% vs. 51%; P<0.001), and it was maintained regardless of patients’ prognosis.