title: Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives.
abstract: OBJECTIVE
  HER2 mutations are identified in approximately 2%of non-small-cell lung cancers (NSCLC). There are few data available that describe the clinical course of patients with HER2-mutated NSCLC.
  
  
  METHODS
  We retrospectively identified 65 NSCLC, diagnosed with a HER2 in-frame insertion in exon 20. We collected clinicopathologic characteristics, patients' outcomes, and treatments.
  
  
  RESULTS
  HER2 mutation was identified in 65 (1.7%) of 3,800 patients tested and was almost an exclusive driver, except for one single case with a concomitant KRAS mutation. Our population presented with a median age of 60 years (range, 31 to 86 years), a high proportion of women (45 women v 20 men; 69%), and a high proportion of never-smokers (n= 34; 52.3%). All tumors were adenocarcinomas and 50% were stage IV at diagnosis. For these latter cases, 22 anti-human epidermal growth factor receptor 2 (HER2) treatments were administered after conventional chemotherapy in 16 patients. Subsequently, four patients experienced progressive disease, seven experienced disease stabilizations, and 11 experienced partial responses (overall response rate, 50%; disease control rate [DCR], 82%). Specifically, we observed a DCR of 93% for trastuzumab-based therapies (n = 15) and a DCR of 100% for afatinib (n = 3) but no response to other HER2-targeted drugs (n = 3). Progression-free survival for patients with HER2 therapies was 5.1 months. Median survival was of 89.6 and 22.9 months for early-stage and stage IV patients, respectively.
  
  
  CONCLUSIONS
  This study, the largest to date dedicated to HER2-mutated NSCLC, reinforces the importance of screening for HER2 mutations in lung adenocarcinomas and suggests the potential efficacy of HER2-targeted drugs in this population.
authors.affiliation: Centre Hospitalier Universitaire de Toulouse, Université de Toulouse III, Toulouse Cedex, France. mazieres.j@chu-toulouse.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Benoit
authors.initials: B
authors.lastname: Lepage
authors.forename: Alexis B
authors.initials: AB
authors.lastname: Cortot
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.forename: Michéle
authors.initials: M
authors.lastname: Beau-Faller
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Hélène
authors.initials: H
authors.lastname: Blons
authors.forename: Audrey
authors.initials: A
authors.lastname: Mansuet-Lupo
authors.forename: Thierry
authors.initials: T
authors.lastname: Urban
authors.forename: Denis
authors.initials: D
authors.lastname: Moro-Sibilot
authors.forename: Eric
authors.initials: E
authors.lastname: Dansin
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouquette
authors.forename: Julie D
authors.initials: JD
authors.lastname: Milia
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000453:epidemiology; D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005602:France / Q000453:epidemiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D016254:Mutagenesis, Insertional; D009367:Neoplasm Staging; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D013557:Switzerland / Q000453:epidemiology; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000077716:Afatinib; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human