Clinical factors associated with treatment outcomes in EGFR mutant non-small cell lung cancer patients with brain metastases: a case-control observational study

BACKGROUND: Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations often develop brain metastases. Treatment with EGFR-tyrosine kinase inhibitors (TKIs) has shown the effectiveness; however, knowledge of the clinical factors associated with outcomes in NSCLC patients with EGFR mutations remains limited. METHODS: Treatment-naive patients diagnosed with advanced non-squamous NSCLC with brain metastases harboring EGFR mutations and treated with an EGFR-TKI as first-line therapy were enrolled with analysis of their medical records. RESULTS: A total of 134 advanced NSCLC patients with brain metastases harboring EGFR mutations received an EGFR-TKI (gefitinib: 62, erlotinib: 49, and afatinib: 23) as the first-line therapy. Sixty-nine had exon 19 deletions (51.5%), and 56 (41.8%) had L858R mutations. There was no statistically significant difference in progression-free survival (PFS) and overall survival (OS) among the EGFR-TKIs. Significantly shorter OS was noted in patients with multiple brain metastases (hazard ratio [HR]: 2.43, p = 0.007), uncommon EGFR mutations (HR: 3.75, p = 0.009), and liver metastases. Thirty-eight patients (29.1%) received brain radiotherapy for brain metastases before disease progression, and had a significantly longer time until intracranial progression. However, the brain radiotherapy had no statistically significant impact on PFS or OS. CONCLUSIONS: Patients with uncommon mutations, multiple brain metastases, and concomitant liver metastases tended to have shorter OS. Brain radiotherapy could delay the time to intracranial disease progression but had no impact on survival. The different first-line EGFR-TKIs achieved similar treatment responses in terms of PFS and OS in the EGFR-mutated NSCLC patients with brain metastases.