Yongmei Liu¹, Qian Zhao², Xiaojuan Zhou³, Yong Xu⁴, Youling Gong⁴,Meijuan Huang⁴, Feng Peng⁴, Lin Zhou⁴, Jiang Zhu⁴, Jin Wang⁴, Li Ren⁴, Mei Hou⁴, You Lu⁴, Yongmei Liu³

¹Department of ThoracicOncology, Cancer Center, West China Hospital, Sichuan University, ²School of Medicine, WestChina Sichuan University, ³Sichuan University,Department of Thorac West China Hospital, ⁴Department of ThoracicOncology,

West China Sichuan University

Objective:Central nervous system (CNS) progressionis frequently detected in patients with favorable initial responses toEpidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs), butdata are incomplete with respect to clinical features and prognostic factors ofCNS failure in this population. Method: We retrospectively evaluated 308advanced Non-Small Cell Lung Cancer (NSCLC) patients treated with first orsecond-line gefitinib for over 6 months. We studied CNS progression of thosepatients, defining this as newly developed CNS metastases or progression ofpreexisting brain lesions after gefitinib treatment. Result: Of the 308patients, 89 with CNS progression after gefitinib initiation were identified.The median time to CNS progression was 12 months (95% CI 10.5-13.5). Forpatients with previous brain metastases, the median time to CNS progression ofpatients with gefitinib and local CNS therapy was significantly longer thanthose treated with gefitinib alone (23.6 months vs. 15.5 months; P=0.014).Patients with L858R mutations were more likely to experience CNS failure thanthose with exon 19 deletions (P=0.05). The median survival time afterCNS progression was 10.4 months (95%CI 7.5-13.3). Localized CNS therapy was theonly independent predictor of overall survival (OS) for these patientsaccording to both univariate and multivariate analysis. In subset analysiswithin patients harboring EGFR common activating mutations, the median OS afterCNS progression of patients harboring L858R mutation are significantly shorterthan those with exon 19 deletions (9.5vs.33.2, P=0.037). Conclusion: Foradvanced NSCLC patients treated successfully with gefitinib, careful monitoringfor CNS failure and localized CNS therapy should be considered for CNSprogression. L858R mutations might be associated with higher risk of CNSprogression and represent a negative prognostic factor, compared with exon 19deletions.

Key Words: Non-small cell lung cancer  gefitinb central nervous