title: The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer.
abstract: OBJECTIVE
  In non-small cell lung cancer (NSCLC), the association between common EGFR mutations (Del EX19/L858R) with EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been well established. However, this has not been investigated for rare EGFR mutations or their impact on treatment response and outcome to EGFR TKIs (primary objective) and chemotherapy (secondary objective).
  
  
  METHODS
  In an observational prospective cohort, we analyzed 188 NSCLC patients from Mexico, Colombia and Costa Rica with EGFR mutations. As a first line of treatment, 66.5% received platinum-based chemotherapy. All patients received TKIs in first-line treatment or after progression to chemotherapy. The clinical-pathological characteristics as well as the f of common and rare EGFR mutations associated with treatment response were analyzed.
  
  
  RESULTS
  Of all patients, 79.5% had common and 20.5% had rare EGFR mutations. Lepidic and acinar adenocarcinomas were associated with common EGFR mutations (p=0.010). Patients with common EGFR mutations had higher response rates to EGFR-TKIs than those who had rare EGFR mutations (63.8 vs 32.4%, p<0.001). Women had increased progression-free survival (PFS) to EGFR-TKIs than men (16.4 vs 9.5 months, p=0.02). The median PFS and overall survival (OS) were better in patients with common EGFR mutations (15.5 vs 3.9 months, p<0.001; and 37.3 vs 17.4 months, p<0.001) respectively.
  
  
  CONCLUSIONS
  Our findings suggested that only patients with rare EGFR mutations could receive platinum-based chemotherapy as a first-line treatment, due to their low response rates and short PFS in response to EGFR-TKIs. Consequently, EGFR-TKIs could be reserved as a second- or third-line treatment. In patients with EGFR mutations, women have better PFS to EGFR-TKIs than men, and rare EGFR mutations are more frequent in high grade adenocarcinomas than in low grade tumors.
authors.affiliation: Thoracic Oncology Unit and Experimental Oncology Laboratory, National Cancer Institute (INCan), México, D.F., Mexico. Electronic address: ogar@unam.mx.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Santa Fe, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Andrés Felipe
authors.initials: AF
authors.lastname: Cardona
authors.affiliation: Medical Oncology, Hospital San Juan de Dios - CCSS, San José, Costa Rica.
authors.forename: Luis
authors.initials: L
authors.lastname: Corrales
authors.affiliation: Thoracic Oncology Unit and Experimental Oncology Laboratory, National Cancer Institute (INCan), México, D.F., Mexico.
authors.forename: Alma Delia
authors.initials: AD
authors.lastname: Campos-Parra
authors.affiliation: Thoracic Oncology Unit and Experimental Oncology Laboratory, National Cancer Institute (INCan), México, D.F., Mexico.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sánchez-Reyes
authors.affiliation: Thoracic Oncology Unit and Experimental Oncology Laboratory, National Cancer Institute (INCan), México, D.F., Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Amieva-Rivera
authors.affiliation: Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: July
authors.initials: J
authors.lastname: Rodríguez
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Santa Fe, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vargas
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Santa Fe, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Hernán
authors.initials: H
authors.lastname: Carranza
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Santa Fe, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Jorge
authors.initials: J
authors.lastname: Otero
authors.affiliation: Catalan Institute of Oncology - ICO Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: Nikki
authors.initials: N
authors.lastname: Karachaliou
authors.affiliation: Laboratory of Translational Cancer Research and Cellular Therapy, Oncology Hospital, Medical Center Siglo XXI, Mexico City, Mexico.
authors.forename: Horacio
authors.initials: H
authors.lastname: Astudillo
authors.affiliation: Catalan Institute of Oncology - ICO Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; 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; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D010984:Platinum; D066246:ErbB Receptors
keywords: Adenocarcinoma lung cancer; Deletion exon 19; EGFR mutations; EGFR-tyrosine kinase inhibitors; L858R mutation