Solange Peters1, Alessandra Curioni-Fontecedro2, Hovav Nechushtan3, Jin-Yuan Shih4, Wei-Yu Liao5, Oliver Gautschi6, Vito Spataro7, Mojca Unk8, James Chih-Hsin Yang9, Robert M Lorence10, Philippe Carrière11, Agnieszka Cseh12, Gee-Chen Chang13. 1. Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: solange.peters@chuv.ch. 2. Department of Hematology and Oncology, Division of Oncology, University Hospital Zurich, Zurich, Switzerland. 3. Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Kiryat Hadassah, Jerusalem, Israel. 4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 5. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. 6. Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland. 7. Department of Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. 8. Department for Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia. 9. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. 10. Oncology Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut. 11. Risk Management Oncology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut. 12. Medical Department, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria. 13. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; and the Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Abstract
INTRODUCTION: Approximately 1% to 4% of NSCLC tumors harbor erb-b2 receptor tyrosine kinase 2 (ERBB2) mutation; there is no approved targeted treatment for this subgroup. METHODS: Patients with stage IV NSCLC that progressed after clinical benefit on erlotinib/gefitinib and/or had activating EGFR or ERBB2 mutations, had exhausted other treatments, and were ineligible for afatinib trials were enrolled in a named patient use program, receiving afatinib 30 to 50 mg/d on a compassionate basis within routine clinical practice. Efficacy and safety were retrospectively assessed in the subgroup with ERBB2 mutation-positive NSCLC. RESULTS: Twenty-eight heavily pretreated patients in the named patient use program had a documented ERBB2 mutation by local testing. Median time-to-treatment failure (TTF; time from treatment initiation to discontinuation for any reason) was 2.9 months; eight patients (29%) had TTF greater than 1 year. Objective response rate was 19% (3 of 16 patients with response data achieved partial response) and disease control rate (DCR) was 69% (11 of 16). Among 12 patients for whom type of ERBB2 mutation was specified, 10 had a p.A775_G776insYVMA insertion in exon 20, four of whom (40%) remained on afatinib for more than 1 year. This subgroup had median TTF of 9.6 months, objective response rate of 33% (two of six), and disease control rate of 100% (six of six). CONCLUSIONS: This analysis of patients treated in clinical practice provides further evidence of the activity of afatinib in ERBB2 mutation-positive NSCLC, and suggests that identification of specific subgroups with certain mutations, such as p.A775_G776ins/YVMA insertion in exon 20, could help optimize outcomes with ErbB2-targeted treatment.
INTRODUCTION: Approximately 1% to 4% of NSCLC tumors harbor erb-b2 receptor tyrosine kinase 2 (ERBB2) mutation; there is no approved targeted treatment for this subgroup. METHODS:Patients with stage IV NSCLC that progressed after clinical benefit on erlotinib/gefitinib and/or had activating EGFR or ERBB2 mutations, had exhausted other treatments, and were ineligible for afatinib trials were enrolled in a named patient use program, receiving afatinib 30 to 50 mg/d on a compassionate basis within routine clinical practice. Efficacy and safety were retrospectively assessed in the subgroup with ERBB2 mutation-positive NSCLC. RESULTS: Twenty-eight heavily pretreated patients in the named patient use program had a documented ERBB2 mutation by local testing. Median time-to-treatment failure (TTF; time from treatment initiation to discontinuation for any reason) was 2.9 months; eight patients (29%) had TTF greater than 1 year. Objective response rate was 19% (3 of 16 patients with response data achieved partial response) and disease control rate (DCR) was 69% (11 of 16). Among 12 patients for whom type of ERBB2 mutation was specified, 10 had a p.A775_G776insYVMA insertion in exon 20, four of whom (40%) remained on afatinib for more than 1 year. This subgroup had median TTF of 9.6 months, objective response rate of 33% (two of six), and disease control rate of 100% (six of six). CONCLUSIONS: This analysis of patients treated in clinical practice provides further evidence of the activity of afatinib in ERBB2 mutation-positive NSCLC, and suggests that identification of specific subgroups with certain mutations, such as p.A775_G776ins/YVMA insertion in exon 20, could help optimize outcomes with ErbB2-targeted treatment.
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