title: Central nervous system progression in advanced non-small cell lung cancer patients with EGFR mutations in response to first-line treatment with two EGFR-TKIs, gefitinib and erlotinib: a comparative study.
abstract: Central nervous system (CNS) brain metastasis of advanced non-small cell lung cancer (NSCLC) patients confers a worse quality of life and prognosis. The efficacy comparison of two first-generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib as first-line treatment for CNS metastasis NSCLC patients with EGFR-sensitizing mutations is yet to be elucidated.
  
  
  
  A retrospective analysis was done on cerebral metastasis rate after erlotinib or gefitinib as first-line treatment for advanced NSCLC patients with EGFR-sensitizing mutations. Time to neurological progression (nTTP) and median progression-free survival (mPFS) were calculated.
  
  
  
  The study involved 279 patients (erlotinib group: 108, gefitinib group: 171). After a median follow-up of 22 months, 27 patients (25%) in the erlotinib group and 60 patients (35.1%) in the gefitinib group showed CNS progression. The HR of CNS progression for erlotinib versus gefitinib was 0.695 [95% confidence interval (CI), 0.406-1.190], suggesting a risk reduction of 30.5% although not achieving statistical significance. The 6-, 12- and 18-month cumulative CNS progression rates were 0.9, 3.7 and 12% for erlotinib compared with corresponding rates of 5.8, 9.4 and 17% for gefitinib (P = 0.181). However, for those patients with preexisting brain metastases prior to EGFR-TKI treatment, erlotinib as first line treatment significantly extended the median nTTP in comparison to gefitinib (30 months vs 15.8 months, p = 0.024).
  
  
  
  Our data show that nTTP can be effectively extended in preexisting brain metastases patients with EGFR-sensitizing mutations initially treated with erlotinib compared with gefitinib. If confirmed, our results indicate that erlotinib may play an important role in controlling CNS progression from EGFR mutation-positive NSCLC.
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Meng-Xia
authors.initials: MX
authors.lastname: Li
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Ruan
authors.affiliation: Department of Oncology, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Yu-Xi
authors.initials: YX
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, People's Republic of China.
authors.forename: Rong-Qing
authors.initials: RQ
authors.lastname: Li
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Lan
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Eighth Department, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, People's Republic of China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Liu
authors.affiliation: Department of Pathology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, People's Republic of China.
authors.forename: Hua-Liang
authors.initials: HL
authors.lastname: Xiao
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People's Republic of China. yangzz1970@163.com.
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage
chemical_list: D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFR mutation; EGFR-TKIs; Erlotinib; Gefitinib; NSCLC