Central nervous system (CNS) progression is frequently detected in patients with favorable initial responses to first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), but data are incomplete with respect to clinical features and prognostic factors of CNS failure in this population. We retrospectively evaluated 420 advanced nonsmall cell lung cancer (NSCLC) patients treated with first-generation EGFR-TKI for over 3 months. We analyzed CNS progression of these patients, defining as newly developed CNS metastases or progression of preexisting brain lesions after EGFR-TKI treatment. Of the 420 patients, 99 (23.6%) with CNS progression after EGFR-TKI initiation were identified. The median time to CNS progression was 12 months (95% confidence interval [CI] 10.5-13.5). Patients with L858R mutation were more likely to experience CNS failure than those with exon 19 deletion (p = 0.008). For patients with previous brain metastases (BM), the median time to CNS progression of patients with EGFR-TKI and local CNS therapy was significantly longer than those treated with EGFR-TKI alone (14.0 months vs. 11.2 months; p = 0.016). The median survival time after CNS progression was 11.2 months (95% CI 8.8-13.5). L858R mutation, multiple BM progression and CNS with other site failures were negative prognostic factor, while localized CNS therapy was the only significant favorable prognostic factor for overall survival after CNS progression. For advanced NSCLC patients treated successfully with first-generation EGFR-TKI, careful monitoring for CNS progression should be considered, especially for those with L858R mutation. Localized CNS therapy should be considered for CNS progression.
Keywords: central nervous system; nonsmall cell lung cancer; secondary brain neoplasms.