The use of upfront epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and deferral of radiotherapy are associated with inferior overall survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) who develop brain metastases, according to a study published in the Journal of Clinical Oncology.1 

Treatment options for brain metastases in patients with EGFR-mutant NSCLC include stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and EGFR TKIs; however, the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR TKIs is unclear.

To determine the optimal treatment approach of this population, investigators analyzed data from 351 patients with EGFR-mutant NSCLC who developed metastases and were treated at 1 of 6 institutions. Researchers did not include patients with prior EGFR TKI use, EGFR TKI resistance mutations, failure to receive an EGFR TKI after SRS or WBRT, or insufficient follow-up.

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Patients were treated with SRS followed by an EGFR TKI, WBRT followed by an EGFR TKI, or an EGFR TKI followed by SRS or WBRT at the time of intracranial progression.

Results showed that median overall survival for patients who received SRS, WBRT, or a TKI first was 46, 30, and 25 months, respectively (P <.001).

After adjusting for confounding factors, investigators found that receipt of SRS vs a TKI, receipt of WBRT vs a TKI, age, performance status, having an EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved survival.

SRS followed by an EGFR TKI resulted in the longest overall survival and allowed patients to avoid potential neurocognitive toxicities associated with WBRT. Patients who received WBRT before a TKI were significantly more likely to have a less favorable prognosis.

The findings ultimately underscore the urgent need for a prospective, randomized clinical trial of SRS followed by an EGFR TKI vs an EGFR TKI followed by SRS at time of intracranial progression in this population.


1. Magnuson WJ, Lester-Coll NH, Wu AJ, et al. Management of brain metastases in tyrosine kinase inhibitor–naïve epidermal growth factor receptor–mutant non–small-cell lung cancer: a retrospective multi-institutional analysis. J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144. [Epub ahead of print]