title: Experience with afatinib in patients with non-small cell lung cancer progressing after clinical benefit from gefitinib and erlotinib.
abstract: BACKGROUND
  Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients receiving afatinib within a compassionate-use program (CUP).
  
  
  METHODS
  Patients with advanced NSCLC progressing after one line or more of chemotherapy and one line or more of EGFR-TKI treatment with either an EGFR mutation or documented clinical benefit were enrolled. Data collection was not monitored or verified by central review. The intention of this CUP was to provide controlled preregistration access to afatinib for patients with life-threatening diseases and no other treatment option.
  
  
  RESULTS
  From May 2010 to October 2013, 573 patients (65% female; median age: 64 years [range: 28-89 years]) were enrolled, with strong participation of community oncologists. Comorbidities were allowed, including second malignancies in 11% of patients. EGFR mutation status was available in 391 patients (72%), and 83% tested mutation positive. Median time to treatment failure (TTF) of 541 patients treated with afatinib was 3.7 months (range: 0.0 to >29.0 months). Median TTF was 4.0 and 2.7 months in patients with adenocarcinomas and squamous cell carcinomas, respectively, and 4.6 months in patients with EGFR-mutated NSCLC. Adverse events were generally manageable.
  
  
  CONCLUSIONS
  Afatinib was able to be given in a real-world setting to heavily pretreated patients with EGFR-mutated or EGFR-TKI-sensitive NSCLC. Acknowledging the constraints of data collection in a CUP, afatinib appears to be safe and to confer some clinical benefit in this population.
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany martin.schuler@uk-essen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Fischer
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Gütz
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kimmich
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Claus-Peter
authors.initials: CP
authors.lastname: Schneider
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Laack
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, Department of Medical Oncology, Klinik Löwenstein, Löwenstein, Germany; Department of Respiratory Medicine, Evangelische· Lungenklinik, Berlin, Germany; Department of Pneumology, Evangelisches Diakonissenkrankenhaus, Leipzig, Germany; Translational Lung Research Center Heidelberg, Heidelberg, Germany; Department of Pneumology and Thoracic Oncology, Klinik Schillerhoehe, Gerlingen, Germany; Department of Hematology and Medical Oncology, Zentralklinik, Bad Berka, Germany; Haemato-Oncology Hamburg, Hamburg, Germany; Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Märten
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D057176:Compassionate Use Trials; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Afatinib; Epidermal growth factor receptor; Erlotinib; Gefitinib; Non-small cell lung cancer