Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 76; no. 1; pp. 123 - 127
• Main Authors: De Grève, J, Teugels, E, Geers, C, Decoster, L, Galdermans, D, De Mey, J, Everaert, H, Umelo, I, Veld, P. In’t, Schallier, D
• Format: Journal Article Web Resource
• Language: English
• Published: Oxford Elsevier Ireland Ltd 01-04-2012; Elsevier
• Subjects: Adenocarcinoma; Adenocarcinoma - diagnosis; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma/diagnosis/drug therapy/genetics; Afatinib; Aged; Amino Acid Sequence; Biological and medical sciences; Epidermal growth factor receptor (EGFR); Female; Hematology, Oncology and Palliative Medicine; Human epidermal growth factor receptor 2 (HER2); Human health sciences; Humans; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms/diagnosis/drug therapy/genetics; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation; Mutation - genetics; Non-small cell lung cancer (NSCLC); Oncologie; Oncology; Pneumology; Prognosis; Protein Kinases - genetics; Pulmonary/Respiratory; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - genetics; Receptor, ErbB-2/antagonists & inhibitors/genetics; Sciences de la santé humaine; Sequence Homology, Amino Acid; Tumors; Tumors of the respiratory system and mediastinum; Adenocarcinoma; Human epidermal growth factor receptor 2 (HER2); Mutation; Afatinib; Epidermal growth factor receptor (EGFR); Non-small cell lung cancer (NSCLC); Human; Lung disease; Enzyme; Respiratory disease; Transferases; Activity; Malignant tumor; Bronchopulmonary adenocarcinoma; non-small cell lung carcinoma; Growth factor receptor; Cancerology; Epidermal growth factor; Kinase; Bronchus disease; Cancer; Non small cell carcinoma; Pneumology
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2012.01.008

Abstract Human epidermal growth factor receptor (HER)2/neu kinase domain mutations are found in approximately 1–4% of lung adenocarcinomas with a similar phenotype to tumors with epidermal growth factor receptor (EGFR) mutations. Afatinib is a potent irreversible ErbB family blocker. We determined the tumor genomic status of the EGFR and HER2 genes in non- or light smokers with lung adenocarcinoma in patients who were entered into an exploratory Phase II study with afatinib. Five patients with a non-smoking history and metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were identified, three of which were evaluable for response. Objective response was observed in all three patients, even after failure of other EGFR- and/or HER2-targeted treatments; the case histories of these patients are described in this report. These findings suggest that afatinib is a potential novel treatment option for this subgroup of patients, even when other EGFR and HER2 targeting treatments have failed.