Abstract
BackgroundCompared with standard chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, data comparing the efficacies of different EGFR−TKIs, especially regarding the presence of brain metastasis, are lacking.MethodsEGFR-TKI naive patients with recurrent or stage IIIB/IV NSCLC harboring EGFR mutations, excluding resistance mutations, were enrolled in this study. We retrospectively determined progression-free survival (PFS) using the Kaplan−Meier method with log-rank test in patients treated with either gefitinib or erlotinib, cumulative incidence of central nervous system (CNS) progression using the Fine and Gray competing risk regression model, and favorable prognostic factors for CNS progression by multivariate analysis.ResultsSeventy-seven EGFR-TKI-naive patients were started on either gefitinib (n = 55) or erlotinib (n = 22) in our hospital from April 2010 to April 2016. Among the patients with brain metastasis, PFS tended to be longer in the erlotinib than in the gefitinib group. In the analysis of cumulative incidence, the probability of CNS progression was lower in the erlotinib group than in the gefitinib group. Particularly, in a subgroup analysis of the patients with brain metastasis, there was a significant difference between the erlotinib and gefitinib groups (hazard ratio 0.25; 95% confidence interval, 0.08–0.81; p = 0.021). Of the prognostic factors for CNS progression evaluated, the absence of brain metastasis before EGFR-TKI therapy and receiving erlotinib (vs gefitinib) had a significantly favorable effect on patient prognosis.ConclusionAlthough this was a retrospective analysis involving a small sample size, erlotinib is potentially more promising than gefitinib for treatment of brain metastasis in patients with EGFR-mutant NSCLC.
Highlights
Compared with standard chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations
As for brain metastasis, more of patients who treated with erlotinib have had brain metastasis (12 [55%]) and received radiation therapy (6 [27%]) prior to EGFR-TKI treatment compared with those treated with gefitinib
In the cumulative incidence analysis, the probability of central nervous system (CNS) progression was lower in the erlotinib group than in the gefitinib group
Summary
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. 40% of patients with non-small-cell lung cancer (NSCLC) develop brain metastasis during the course of their disease [1]. The risk of brain metastasis is greater in patients harboring epidermal growth factor receptor (EGFR) mutations [2]. Several case reports and studies involving small patient series indicated successful treatment of brain metastasis using EGFR-TKIs [7,8,9,10]. The aim of our study was to evaluate retrospectively the effect of two first-generation EGFR-TKIs (gefitinib and erlotinib) on brain metastasis in patients with NSCLC harboring EGFR mutations
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