title: Clinical efficacy of first-generation EGFR-TKIs in patients with advanced non-small-cell lung cancer harboring EGFR exon 20 mutations.
abstract: OBJECTIVE
  Subsets of non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations carry uncommon subtypes. We evaluated the efficacy of first-generation EGFR-tyrosine kinase inhibitors (TKIs; erlotinib, gefitinib, and icotinib) in patients with non-small-cell lung cancer carrying insertions and T790M and S768I mutations in EGFR exon 20.
  
  
  METHODS
  Patients carrying EGFR exon 20 insertion/T790M/S768I mutations and treated with EGFR-TKIs were evaluated from 2005 to 2014 in Zhejiang Cancer Hospital. The efficacy was evaluated using the Kaplan-Meier method and compared with the log-rank test.
  
  
  RESULTS
  Sixty-two patients with exon 20 insertion/T790M/S768I mutations were enrolled. Mutations including exon 20 insertions and T790M and S768I mutations were observed in 29, 23, and ten patients, respectively. In total, the response rate and median progression-free survival (PFS) were 8.1% and 2.1 months, respectively. Patients with S768I mutation manifested the longest median PFS (2.7 months), followed by those with T790M (2.4 months) and exon 20 insertions (1.9 months; P=0.022). Patients with complex mutations show a better PFS than those with single mutations (2.7 months vs 1.9 months; P=0.034).
  
  
  CONCLUSIONS
  First-generation EGFR-TKIs are less effective in patients with exon 20 uncommon mutations than in those with common mutations. Patients with complex mutations benefited more from first-generation EGFR-TKIs than those with single mutations.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Chemotherapy.
authors.forename: Zhengbo
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Cheng
keywords: EGFR mutations; epidermal growth factor receptor; exon 20; non-small cell lung cancer; tyrosine kinase inhibitor