title: Different EGFR Gene Mutations in Exon 18, 19 and 21 as Prognostic and Predictive Markers in NSCLC: A Single Institution Analysis.
abstract: BACKGROUND
  Mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) predict longer overall survival (OS) and response to EGFR tyrosine kinase inhibitors (TKIs). The clinical relevance of different mutations in terms of response to TKIs and prognosis is still unclear.
  
  
  OBJECTIVE
  The aims of the present study were to assess the relationship between mutations in exon 18, 19 and 21 in patients treated with TKIs and their clinical outcomes, and evaluate the role of specific point mutations.
  
  
  METHODS
  We included in this analysis 55 patients with metastatic NSCLC and mutations in exon 18, 19 and 21, treated in our center between 2004 and 2014. All patients received treatment with TKIs in first and/or subsequent lines. Endpoints analyzed were OS (primary) and time to progression (TTP) (secondary), according to exon mutations and specific point mutations.
  
  
  RESULTS
  A strong negative prognostic association for OS (p = 0.02) and TTP (p = 0.03) was found for exon 18 mutations compared with exon 19 deletions . A trend toward a longer median OS was observed in exon 19 deletions versus exon 21 point mutations (+6.6 months), although more exon 19-mutated patients had brain metastases at diagnosis. Comparing each mutation, p.E746_A750del and p.E746_T751del of exon 19 and p.L858R mutation of exon 21, a trend toward improved OS in p.E746_A750del was found.
  
  
  CONCLUSIONS
  In this analysis, exon 19 deletions were associated with better outcomes, despite a higher percentage of brain metastases in this group. The prognostic relevance of p.E746_A750del requires further studies.
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy. sbrn.rossi85@gmail.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: D'Argento
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Basso
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Strippoli
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dadduzio
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cerchiaro
authors.affiliation: Department of Pathology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cassano
authors.affiliation: Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
mesh_terms: D000077716:Afatinib; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D005091:Exons; D005260:Female; D000077156:Gefitinib; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D000068437:Pemetrexed / Q000494:pharmacology; D011379:Prognosis; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000494:pharmacology; D012189:Retrospective Studies; D043823:Taxoids / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D005819:Genetic Markers; D011799:Quinazolines; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib; D000093542:Gemcitabine