title: Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort.
abstract: BACKGROUND
  HER2 mutations have been identified as oncogenic drivers in lung cancers and are found in 1-2% of lung adenocarcinomas. There is, to date, no standard of care for these patients. We thus aim to study the therapeutic outcomes of patients harboring HER2 mutations and establish the efficacy of various drug regimens.
  
  
  METHODS
  This retrospective cohort study in European centers assessed patients with advanced non-small-cell lung cancer (NSCLC), a known HER2 exon-20 insertion, treated with chemotherapy and/or HER2-targeted drugs.
  
  
  RESULTS
  We identified 101 eligible patients from 38 centers: median age 61 years (range: 30-87), 62.4% women, 60.4% never-smokers. All tumors were adenocarcinomas. Concomitant EGFR mutations, ALK translocations, and ROS translocations were observed in 5, 1, and 1 patients, respectively. The median number of treatment lines was 3 (range: 1-11). The median overall survival was 24 months. Overall response rate (ORR) and the median progression-free survival (PFS) with conventional chemotherapy (excluding targeted therapies) were 43.5% and 6 months in first-line (n = 93), and 10% and 4.3 months in second-line (n = 52) therapies. Sixty-five patients received HER2-targeted therapies: trastuzumab = 57, neratinib = 14, afatinib = 9, lapatinib = 5, T-DM1 = 1. ORR was 50.9% and PFS was 4.8 months with trastuzumab or T-DM1.
  
  
  CONCLUSIONS
  This series shows the chemosensitivity of HER2-driven NSCLC, and the potential interest of HER2-targeted agents. Our results should help to define the best therapeutic strategy for these patients and to orient future clinical trials.
authors.affiliation: Thoracic Oncology Unit, Larrey Hospital, Centre Hospitalier Universitaire de Toulouse, Toulouse University III (Paul Sabatier), Toulouse mazieres.j@chu-toulouse.fr.
authors.forename: J
authors.initials: J
authors.lastname: Mazières
authors.affiliation: Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille.
authors.forename: F
authors.initials: F
authors.lastname: Barlesi
authors.affiliation: Clinical Research Unit, Biostatistics, Cancer University Institute of Toulouse Oncopole, Toulouse.
authors.forename: T
authors.initials: T
authors.lastname: Filleron
authors.affiliation: Thoracic Oncology Section, Gustave Roussy Cancer Campus, Villejuif.
authors.forename: B
authors.initials: B
authors.lastname: Besse
authors.affiliation: Pulmonology Department, Centre hospitalier intercommunal, Créteil.
authors.forename: I
authors.initials: I
authors.lastname: Monnet
authors.affiliation: Chest Department, Strasbourg University Hospital, Strasbourg, France.
authors.forename: M
authors.initials: M
authors.lastname: Beau-Faller
authors.affiliation: Medical Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Peters
authors.affiliation: Medical Oncology Department, Centre Oscar Lambret, Lille, France.
authors.forename: E
authors.initials: E
authors.lastname: Dansin
authors.affiliation: Department of Oncology and Hematology, Cantonal Hospital of St Gallen, St Gallen.
authors.forename: M
authors.initials: M
authors.lastname: Früh
authors.affiliation: Department of Medical Oncology, Kantonsspital Winterthur, Winterthur, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Pless
authors.affiliation: Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Rosell
authors.affiliation: Pulmonary Medicine Unit, AP-HP, Hôpital Tenon, Paris.
authors.forename: M
authors.initials: M
authors.lastname: Wislez
authors.affiliation: Medical Oncology Department, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez.
authors.forename: P
authors.initials: P
authors.lastname: Fournel
authors.affiliation: Pulmonology Department, Centre Hospitalier Régional Universitaire, Hôpital Jean Minjoz, Besançon, France.
authors.forename: V
authors.initials: V
authors.lastname: Westeel
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: Pulmonology Department, Centre Hospitalier Universitaire, Lille.
authors.forename: A
authors.initials: A
authors.lastname: Cortot
authors.affiliation: Department of Thoracic Oncology, Centre Hospitalier Universitaire, Grenoble, France.
authors.forename: D
authors.initials: D
authors.lastname: Moro-Sibilot
authors.affiliation: Thoracic Oncology Unit, Larrey Hospital, Centre Hospitalier Universitaire de Toulouse, Toulouse University III (Paul Sabatier), Toulouse.
authors.forename: J
authors.initials: J
authors.lastname: Milia
authors.affiliation: Medical Oncology, Cantonal Hospital Luzern, Luzern, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Gautschi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005060:Europe; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D011799:Quinazolines / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D000068878:Trastuzumab / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000077716:Afatinib; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000077341:Lapatinib; D011799:Quinazolines; D011804:Quinolines; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000626173:ALK protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C487932:neratinib
keywords: HER2; biomarker; chemotherapy; lung cancer; trastuzumab