title: Clinical likelihood of sporadic primary EGFR T790M mutation in EGFR-mutant lung cancer.
abstract: BACKGROUND
  It has been reported that the presence of pretreatment EGFR T790M mutation may reduce the efficacy to EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancer. However, clinicopathologic features related to the likelihood of T790M mutation before treatment remains unknown.
  
  
  METHODS
  DNA from 124 pretreatment tissue samples from patients with advanced non-small-cell lung cancer carrying sensitive EGFR mutations was genotyped for EGFR T790M mutation with mass spectrometry. We compared the characteristics of 24 T790M patients and 100 patients with no or a low-level T790M mutation.
  
  
  RESULTS
  There were no differences in age, sex, histology, or initial stage between T790M and non/low T790M groups. However, there were significantly more never-smokers in the T790M group (P = .017). Brain metastasis was also more common in the T790M group (P = .036). The response rates to platinum, taxane, gemcitabine, and pemetrexed did not differ between the 2 groups. In the T790M group, the response rates were not significantly different among the 4 cytotoxic drugs (P = .809). The median time to progression during EGFR-TKI therapy was shorter in the T790M group than in the non/low T790M group (4.1 vs. 11.5 months, respectively; P < .001). The median overall survival from the start of first-line treatment of advanced disease was similar in both groups (31.5 vs. 36.0 months, respectively; P = .310).
  
  
  CONCLUSIONS
  The clinical features of EGFR T790M-mutant lung cancer were similar to those of sensitive EGFR-mutant lung cancer, except for the overrepresentation of never-smokers and brain metastasis.
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea. Electronic address: yjlee@ncc.re.kr.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.affiliation: Cancer Genomics Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Hwang
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Tak
authors.initials: T
authors.lastname: Yun
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D004247:DNA / Q000032:analysis*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D004247:DNA; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Drug resistance; Drug sensitivity; EGFR mutation; EGFR tyrosine kinase inhibitor; Non–small-cell lung cancer; Sequencing