title: Possible differential EGFR-TKI efficacy among exon 19 deletional locations in EGFR-mutant non-small cell lung cancer.
abstract: BACKGROUND
  Exon 19 deletion mutations (Del-19s) and the exon 21 L858R point mutation are the most common epidermal growth factor receptor (EGFR) mutations. In Del-19, several subtypes actually exist, consisting of the deletional location with or without amino acid insertion/substitution. Little evidence has been described whether the Del-19 subtype affects EGFR-tyrosine kinase inhibitor (TKI) efficacy.
  
  
  METHODS
  Between December 2005 and July 2012, we investigated 105 patients harboring a Del-19 who had received EGFR-TKIs. Efficacies of EGFR-TKIs such as response rate (RR), progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated among various patient characteristics.
  
  
  RESULTS
  Among these 105 patients with Del-19s, 78 (74%) patients had a deletion from E746 (Del-E746), and 27 (26%) exhibited a deletion from L747 (Del-L747). Median PFS of Del-E746 (11.7 months, 95% confidence interval [CI]: 9.3-15.6) was significantly longer than Del-L747 (10.0 months, 95% CI: 6.4-12.7) (p=0.022). Insertions/substitutions were found in 19 patients (18%), and 91 patients (82%) were without insertions/substitutions. Median PFS without insertions/substitutions (11.7 months, 95% CI 9.3-15.2) was significantly longer than with insertions/substitutions (10.0 months, 95% CI: 4.0-10.6) (p=0.024). No relationships were found for RR among all patient characteristics. In multivariate analysis, performance status (PS) (0/1 vs. 2/3) and initial deletion site (Del-E746 vs. Del-L747) were significant factors for longer PFS, whereas PS, gender (male vs female) and histology (adeno vs squamous) for longer OS.
  
  
  CONCLUSIONS
  Our data indicated better efficacy of EGFR-TKI in Del-E746 than Del-L747. Deletional locations may affect EGFR-TKI efficacy.
authors.affiliation: Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kaneda
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan. Electronic address: a-hata@fbri.org.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.affiliation: Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tomioka
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D017384:Sequence Deletion; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: EGFR mutation; EGFR-TKI; Exon 19 deletion; Insertion; Progression-free survival; Subtype