title: Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.
abstract: OBJECTIVE
  The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients.
  
  
  METHODS
  All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations.
  
  
  RESULTS
  From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%).
  
  
  CONCLUSIONS
  The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in Spain (all histologies) is consistent with previous published data in Caucasian patients. When a sample is available, EGFR mutation testing is feasible in over 90% of cases, and may therefore be suitable for routine clinical practice. CLINICALTRIALS.
  NCT01081496.
authors.affiliation: Hospital Universitario Central de Asturias, Department of Medical Oncology, C/ Julian Claveria s/n, 33006 Oviedo, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Esteban
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Department of Medical Oncology, C/ Mas Casanovas 90, 08025 Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Majem
authors.affiliation: Hospital de Navarra, Department of Medical Oncology, C/ de irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martinez Aguillo
authors.affiliation: Hospital General Universitario de Elche, Department of Medical Oncology, Camino de la Almazara, 11, Elche 03203, Alicante, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Martinez Banaclocha
authors.affiliation: Fundación Jiménez Díaz, Department of Medical Oncology, Avda. Reyes Catolicos 2, 28040 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Dómine
authors.affiliation: Complejo Hospitalario Universitario de Albacete, Department of Medical Oncology, C/ Hermanos Falcó 37, 02006 Albacete, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Gómez Aldaravi
authors.affiliation: Hospital Arnau de Vilanova de Valencia, Department of Medical Oncology, C/ San Clemente 12, 46015 Valencia, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Juan
authors.affiliation: AstraZeneca Farmaceutica Spain S.A., C/ Serrano Galvache, 56, 28033 Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Cajal
authors.affiliation: AstraZeneca Farmaceutica Spain S.A., C/ Serrano Galvache, 56, 28033 Madrid, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Gonzalez Arenas
authors.affiliation: Hospital Puerta de Hierro de Madrid, Department of Medical Oncology, C/ Manuel de Falla, 1, 28222 Majadahonda, Madrid, Spain. Electronic address: mprovenciop@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Provencio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D015995:Prevalence; D012307:Risk Factors; D013030:Spain
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Carcinoma; Epidermal growth factor; Genetic testing; Mutation; Non-small-cell lung; Receptor