title: EGFR Mutation Subtypes Influence Survival Outcomes following First-Line Gefitinib Therapy in Advanced Asian NSCLC Patients.
abstract: Activating mutations in the EGFR gene have been shown to confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced NSCLC. However, wide interpatient variability in treatment outcomes in response to EGFR tyrosine kinase inhibitors in these patients remains unaccounted for. This study aimed to evaluate the influence of EGFR mutation types and subtypes on survival outcomes in advanced Asian patients with NSCLC receiving first-line gefitinib therapy.
  
  
  
  Patients with stage IIIB or IV NSCLC who were harboring EGFR mutations, receiving first-line gefitinib treatment, and of Asian descent (N = 383) were evaluated. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Log-rank tests and Cox proportional hazards models were implemented to evaluate the differences in PFS and OS.
  
  
  
  Significant differences in PFS were observed between patients carrying EGFR mutations in exons 18, 19, 20, and 21, with patients carrying EGFR exon 19 mutations having the longest median PFS (overall p = 8.88 × 10-15). Comparison of PFS among the five different exon 19 mutation subtypes and among the two exon 19 deletion start codons did not reveal any significant differences. No significant difference was observed in OS among patients carrying EGFR mutations on different exons (overall p = 0.054); however, OS was found to be significantly different among the various subtypes of exon 19 mutations, with the 15-nucleotide deletion "non-ELREA" group having the shortest OS of 11.3 months (overall p = 0.025).
  
  
  
  EGFR mutation types and subtypes significantly influence survival outcomes in patients with advanced NSCLC who are receiving first-line gefitinib treatment.
authors.affiliation: Clinical Pharmacology, SingHealth, Singapore.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sutiman
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Shao Weng
authors.initials: SW
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Wan Teck
authors.initials: WT
authors.lastname: Lim
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Quan Sing
authors.initials: QS
authors.lastname: Ng
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Amit
authors.initials: A
authors.lastname: Jain
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Mei Kim
authors.initials: MK
authors.lastname: Ang
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Wan Ling
authors.initials: WL
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Chee Keong
authors.initials: CK
authors.lastname: Toh
authors.affiliation: Clinical Pharmacology, SingHealth, Singapore; Laboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore; Office of Clinical Sciences, Duke-National University of Singapore Medical School, Singapore. Electronic address: ctebal@nccs.com.sg.
authors.forename: Balram
authors.initials: B
authors.lastname: Chowbay
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality* / Q000556:secondary; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Asians; EGFR mutation subtypes; NSCLC; Survival