title: Sequential treatment of tyrosine kinase inhibitors and chemotherapy for EGFR-mutated non-small cell lung cancer: a meta-analysis of Phase III trials.
abstract: BACKGROUND
  This aim of this study was to compare the efficacy of first-line tyrosine kinase inhibitor therapy followed, upon progression, by chemotherapy with the reverse sequence in patients with EGFR-mutated non-small cell lung cancer (NSCLC) in terms of overall survival.
  
  
  METHODS
  We performed a meta-analysis of studies that met the following criteria: Phase III clinical trial comparing the sequencing of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors with chemotherapy in the treatment of advanced EGFR-mutated NSCLC; activating mutations reported; and availability of hazard ratio estimates with 95% confidence intervals (CIs) for overall survival.
  
  
  RESULTS
  Six clinical trials were included in this study. The pooled hazard ratio for overall survival of the EGFR-mutated population that completed sequential treatment was 1.03 (95% CI 0.86-1.22, P=0.776). There was no statistically significant heterogeneity between the studies (tau(2) =0; I(2)=0, 95% CI 0-0.37, P=0.548). Evidence of marked publication bias for the two treatment sequences was insufficient (P=0.145).
  
  
  CONCLUSIONS
  In patients with advanced NSCLC and activating EGFR mutations, first-line chemotherapy followed upon progression by a tyrosine kinase inhibitor was not inferior in terms of overall survival compared with the inverse sequence. This may serve as an indication that chemotherapy could be employed initially if mutation testing results are unavailable.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, People's Republic of China.
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, People's Republic of China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, People's Republic of China.
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, People's Republic of China.
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Biostatistics, School of Public Health, Fudan University, People's Republic of China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biostatistics, School of Public Health, Fudan University, People's Republic of China.
authors.forename: Naiqing
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology and Biostatistics, Institute of Medical Science, Shanghai Jiaotong University School of Medicine, People's Republic of China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Song
authors.affiliation: ProMed Cancer Centers, Shanghai, People's Republic of China.
authors.forename: David
authors.initials: D
authors.lastname: Garfield
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, People's Republic of China.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
keywords: EGFR mutation; chemotherapy; clinical trial; non-small cell lung cancer; tyrosine kinase inhibitor