title: Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations.
abstract: OBJECTIVE
  To investigate the clinical features of patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors (TKIs) in these patients.
  
  
  METHODS
  We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.
  
  
  RESULTS
  Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma (3.9%), adenosquamous carcinoma (2.3%), large cell carcinoma (0.8%), and composite neuroendocrine carcinoma (1.6%). Single mutations accounted for 75.0% (96/128), including G719X (29.7%), S768I (18.0%), 20 exon insertion (13.3%), L861Q (12.5%),De novoT790M (0.8%), and T725 (0.8%). Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate (ORR) was 20.0%, the disease control rate (DCR) was 85.0%, and the progression-free survival (PFS) was 6.4 [95% confidence interval (95% CI), 4.8-7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861Q subtypes showed that ORR was 21.2% (7/33), the DCR was 93.9% (31/33), and PFS was 7.6 (95% CI, 5.8-9.4) months. Patients with exon 20 insertion mutation andDe novoT790M experienced rapid disease progression with PFS no more than 2.7 months.
  
  
  CONCLUSIONS
  Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Beijing Hospital, National Center of Gerontology, Beijing 100730, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
keywords: EGFR; Non-small cell lung cancer; target therapy; uncommon mutation