title: Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP).
abstract: BACKGROUND
  Previously, we reported the frequency of epidermal growth factor receptor (EGFR) and KRAS mutations in nonsmall-cell lung cancer (NSCLC) patients in Latin America. The EGFR mutation frequency was found between Asian (40%) and Caucasian (15%) populations. Here, we report the updated distribution of NSCLC mutations.
  
  
  METHODS
  A total of 5738 samples from NSCLC patients from Argentina (1713), Mexico (1417), Colombia (1939), Peru (393), Panama (174), and Costa Rica (102) were genotyped for EGFR and KRAS.
  
  
  RESULTS
  The median patient age was 62.2 ± 12.3 years; 53.5% were women, 46.7% had a history of smoking, and 95.2% had adenocarcinoma histology. The frequency of EGFR mutations was 26.0% (95% confidence interval [CI], 24.9-27.1; Argentina, 14.4% [12.8-15.6]; México, 34.3% [31.9-36.7]; Colombia, 24.7% [22.8-26.6]; Peru, 51.1% [46.2-55.9]; Panamá, 27.3 [20.7-33.9]; and Costa Rica, 31.4% [22.4-40.4]). The frequency of KRAS mutations was 14.0% (9.1-18.9). In patients with adenocarcinoma, EGFR mutations were independently associated with gender (30.7% females vs. 18.4% males; p < 0.001), nonsmoker status (27.4% vs. 17.1%, p < 0.001), ethnicity (mestizo/indigenous, 35.3% vs. Caucasian, 13.7%, p < 0.001), and the absence of KRAS mutation (38.1% vs. 4.7%; p < 0.001). The overall response rate to EGFR tyrosine kinase inhibitors was 60.6% (95% CI, 52-69), with a median progression-free survival and overall survival of 15.9 (95% CI, 12.420.6) and 32 months (95% CI, 26.5-37.6), respectively.
  
  
  CONCLUSIONS
  Our findings support the genetic heterogeneity of NSCLC in Latin America, confirming that the frequency of EGFR mutations is intermediate between that observed in the Asian and Caucasian populations.
authors: Thoracic Oncology Clinic and Experimental Oncology Laboratory, Instituto Nacional de Cancerologia de México, México D.F., México. Electronic address: ogar@unam.mx.
authors: Oscar
authors: O
authors: Arrieta
authors: Clinical and Translational Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
authors: Andrés F
authors: AF
authors: Cardona
authors: Department of Oncology, Alexander Fleming Institute, Buenos Aires, Argentina; Oncología Médica, Hospital San Juan de Dios, San José, Costa Rica.
authors: Claudio
authors: C
authors: Martín
authors: Department of Clinical Oncology, Instituto de Enfermedades Neoplásicas, Perú.
authors: Luis
authors: L
authors: Más-López
authors: Oncología Médica, Hospital San Juan de Dios, San José, Costa Rica.
authors: Luis
authors: L
authors: Corrales-Rodríguez
authors: Cátedra de Farmacología, Facultad de Farmacia y Bioquimica, Universidad de Buenos, Fundación Investigar, Buenos Aires, Argentina; Oncología Médica, Hospital San Juan de Dios, San José, Costa Rica.
authors: Guillermo
authors: G
authors: Bramuglia
authors: Instituto Oncológico Nacional, Ancón, Panamá.
authors: Omar
authors: O
authors: Castillo-Fernandez
authors: Broad Institute of Harvard, Massachusetts Institute of Technology, Cambridge, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Matthew
authors: M
authors: Meyerson
authors: Thoracic Oncology Clinic and Experimental Oncology Laboratory, Instituto Nacional de Cancerologia de México, México D.F., México.
authors: Eduardo
authors: E
authors: Amieva-Rivera
authors: Thoracic Oncology Clinic and Experimental Oncology Laboratory, Instituto Nacional de Cancerologia de México, México D.F., México.
authors: Alma Delia
authors: AD
authors: Campos-Parra
authors: Clinical and Translational Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
authors: Hernán
authors: H
authors: Carranza
authors: Department of Clinical Oncology, Instituto de Enfermedades Neoplásicas, Perú.
authors: Juan Carlos
authors: JC
authors: Gómez de la Torre
authors: Cátedra de Farmacología, Facultad de Farmacia y Bioquimica, Universidad de Buenos, Fundación Investigar, Buenos Aires, Argentina.
authors: Yanina
authors: Y
authors: Powazniak
authors: Centro Médico Nacional 20 de Noviembre de México, ISSSTE, México D.F., México.
authors: Fernando
authors: F
authors: Aldaco-Sarvide
authors: Clinical and Translational Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
authors: Carlos
authors: C
authors: Vargas
authors: Cátedra de Farmacología, Facultad de Farmacia y Bioquimica, Universidad de Buenos, Fundación Investigar, Buenos Aires, Argentina.
authors: Mariana
authors: M
authors: Trigo
authors: Centro Médico Nacional 20 de Noviembre de México, ISSSTE, México D.F., México.
authors: Manuel
authors: M
authors: Magallanes-Maciel
authors: Clinical and Translational Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
authors: Jorge
authors: J
authors: Otero
authors: Thoracic Oncology Clinic and Experimental Oncology Laboratory, Instituto Nacional de Cancerologia de México, México D.F., México.
authors: Roberto
authors: R
authors: Sánchez-Reyes
authors: Departament of Medicine, Hospital de Clínicas UdelaR, Montevideo, Uruguay; Clínica Del Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires.
authors: Mauricio
authors: M
authors: Cuello
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D044467:American Indian or Alaska Native / Q000235:genetics; D001118:Argentina; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D003105:Colombia; D003364:Costa Rica; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008800:Mexico; D008875:Middle Aged; D059645:Mutation Rate; D010176:Panama; D010568:Peru; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking / Q000235:genetics; D015996:Survival Rate; D044465:White People / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)