J Mazières1, F Barlesi2, T Filleron3, B Besse4, I Monnet5, M Beau-Faller6, S Peters7, E Dansin8, M Früh9, M Pless10, R Rosell11, M Wislez12, P Fournel13, V Westeel14, F Cappuzzo15, A Cortot16, D Moro-Sibilot17, J Milia18, O Gautschi19. 1. Thoracic Oncology Unit, Larrey Hospital, Centre Hospitalier Universitaire de Toulouse, Toulouse University III (Paul Sabatier), Toulouse mazieres.j@chu-toulouse.fr. 2. Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille. 3. Clinical Research Unit, Biostatistics, Cancer University Institute of Toulouse Oncopole, Toulouse. 4. Thoracic Oncology Section, Gustave Roussy Cancer Campus, Villejuif. 5. Pulmonology Department, Centre hospitalier intercommunal, Créteil. 6. Chest Department, Strasbourg University Hospital, Strasbourg, France. 7. Medical Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. 8. Medical Oncology Department, Centre Oscar Lambret, Lille, France. 9. Department of Oncology and Hematology, Cantonal Hospital of St Gallen, St Gallen. 10. Department of Medical Oncology, Kantonsspital Winterthur, Winterthur, Switzerland. 11. Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Barcelona, Spain. 12. Pulmonary Medicine Unit, AP-HP, Hôpital Tenon, Paris. 13. Medical Oncology Department, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez. 14. Pulmonology Department, Centre Hospitalier Régional Universitaire, Hôpital Jean Minjoz, Besançon, France. 15. Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy. 16. Pulmonology Department, Centre Hospitalier Universitaire, Lille. 17. Department of Thoracic Oncology, Centre Hospitalier Universitaire, Grenoble, France. 18. Thoracic Oncology Unit, Larrey Hospital, Centre Hospitalier Universitaire de Toulouse, Toulouse University III (Paul Sabatier), Toulouse. 19. Medical Oncology, Cantonal Hospital Luzern, Luzern, Switzerland.
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. PATIENTS AND 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. CONCLUSION: 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.
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. PATIENTS AND 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. CONCLUSION: 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.
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