title: Optimized selection of three major EGFR-TKIs in advanced EGFR-positive non-small cell lung cancer: a network meta-analysis.
abstract: BACKGROUND
  To answer which epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the best choice for advanced non-small cell lung cancer (NSCLC) EGFR mutants.
  
  
  RESULTS
  16 phase III randomized trials involving 2962 advanced NSCLC EGFR mutants were enrolled. Multiple treatment comparisons showed different EGFR-TKIs shared equivalent curative effect in terms of all outcome measures among the overall, chemo-naïve and previously treated patients. Rank probabilities showed that erlotinib and afatinib had potentially better efficacy compared with gefitinib in both of the overall and chemo-naïve patients. Potentially survival benefit of erlotinib was also observed in previously treated patients compared with gefitinib. Additionally, EGFR-TKI showed numerically greater survival benefit in 19 Del compared with chemotherapy, while it was opposite in 21 L858R. Furthermore, afatinib, erlotinib and gefitinib had high, moderate and low risk of rash & diarrhea, respectively, while the occurrence of elevated liver transaminase was more common in gefitinib.
  
  
  METHODS
  Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were extracted from included studies. Efficacy and toxicity of all included treatments were integrated by network meta-analyses.
  
  
  CONCLUSIONS
  Our study indicated a high efficacy-high toxicity pattern of afatinib, a high efficacy-moderate toxicity pattern of erlotinib and a medium efficacy-moderate toxicity pattern of gefitinib. Recommended EGFR-TKI should be suggested according to patients' tolerability and therapeutic efficacy in clinical practice. Moreover, the treatment for advanced EGFR-positive NSCLC might be different between 19 Del and 21 L858R.
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.|Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Kang
authors.affiliation: Lau Luen Hung Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Xue
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Zhihuang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR-TKI; NSCLC; afatinib; erlotinib; gefitinib