Abstract
BackgroundNon-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.MethodsTreatment-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.ResultsA 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.ConclusionsPatients 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.
Highlights
Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations often develop brain metastases
Among the EGFR-tyrosine kinase inhibitors (TKIs), the first-generation EGFRTKIs gefitinib and erlotinib are inherently different in their method of action from the second-generation EGFR-TKI afatinib, with the former reversibly binding to cause the inhibition of EGFR signaling and the latter irreversibly blocking the ErbB family of receptors
Patient characteristics From May 1, 2013, to May 31, 2016, 658 patients with stage IIIB or IV lung cancer received an EGFR-TKI as first-line therapy
Summary
Patient characteristics From May 1, 2013, to May 31, 2016, 658 patients with stage IIIB or IV lung cancer received an EGFR-TKI as first-line therapy. Patients with multiple extrathoracic metastases in one or more organs, which is known as M1c disease according to the eighth edition of the TNM staging system [23], had shorter median OS, but the difference was not statistically significant (36.9 months, 95% CI: 29.00 to 53.50, p for log-rank test = 0.400, Fig. 2f; Table 3). Patients with intracranial progression had longer OS than those with only extracranial progression, but the difference was not statistically significant (median: 53.5 months, 95% CI: 32.00 to 60.00, p for log-rank test = 0.101, Fig. 2i). The median times to intracranial PD for gefitinib, erlotinib, and afatinib were 23.6, 27.8, and 17.2 months, respectively, but the differences in these median times to intracranial PD were not significant (Table 2).
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