An open label phase II study evaluating first-line EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer patients with tumors showing high EGFR gene copy number
| Autor: | Magdalena Ratajska, Wojciech Biernat, Krzysztof Konopa, Aleksandra Szczesna, Jacek Jassem, Ewa Szutowicz-Zielińska, Małgorzata Suszko-Każarnowicz, Renata Duchnowska, Rafal Dziadziuszko, Aleksander Sowa, Anna Kowalczyk, Janusz Limon, Tomasz Burzykowski |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Male Pathology erlotinib Lung Neoplasms Gene Dosage Phases of clinical research Kaplan-Meier Estimate medicine.disease_cause 0302 clinical medicine Carcinoma Non-Small-Cell Lung Medicine Epidermal growth factor receptor Prospective Studies Erlotinib Hydrochloride In Situ Hybridization Fluorescence Aged 80 and over education.field_of_study biology Middle Aged ErbB Receptors Treatment Outcome 030220 oncology & carcinogenesis Female Erlotinib KRAS medicine.drug gene copy number Adult Diarrhea Proto-Oncogene Proteins B-raf medicine.medical_specialty Population Gene dosage Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Internal medicine Humans Lung cancer education neoplasms Protein Kinase Inhibitors non-small cell lung cancer Aged business.industry Exanthema medicine.disease respiratory tract diseases 030104 developmental biology Mutation biology.protein epidermal growth factor receptor Clinical Research Paper business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Ewa Szutowicz-Zielinska 1,* , Krzysztof Konopa 1,* , Anna Kowalczyk 1 , Malgorzata Suszko-Kazarnowicz 2 , Renata Duchnowska 3 , Aleksandra Szczesna 4 , Magdalena Ratajska 5 , Aleksander Sowa 6 , Janusz Limon 5 , Wojciech Biernat 7 , Tomasz Burzykowski 8 , Jacek Jassem 1 and Rafal Dziadziuszko 1 1 Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland 2 Department of Oncology, The Centre for Pulmonary Diseases Olsztyn, Poland 3 Department of Oncology, Military Institute of Medicine, Warsaw, Poland 4 Department of Lung Diseases, Mazovian Centre for Treatment of Lung Diseases and Tuberculosis, Otwock, Poland 5 Department of Biology and Genetics, Medical University of Gdansk, Poland 6 Roche, Poland 7 Department of Pathomorphology, Medical University of Gdansk, Poland 8 Interuniversity Institute of Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium * Ewa Szutowicz-Zielinska and Krzysztof Konopa contributed equally to this study Correspondence to: Ewa Szutowicz-Zielinska, email: // Keywords : non-small cell lung cancer, epidermal growth factor receptor, gene copy number, erlotinib Received : July 15, 2016 Accepted : October 12, 2016 Published : December 04, 2016 Abstract Background: First-line treatment with epidermal growth factor receptor (EGFR) inhibitors in NSCLC is effective in patients with activating EGFR mutations. The activity of erlotinib in patients harboring high EGFR gene copy number has been considered debatable. Patients and Methods: A multicenter, open-label, single-arm phase II clinical trial was performed to test the efficacy of erlotinib in the first-line treatment of NSCLC patients harboring high EGFR gene copy number defined as ≥4 copies in ≥40% of cells. Findings: Between December 2007 and April 2011, tumor samples from 149 subjects were screened for EGFR gene copy number by fluorescence in-situ hybridization (FISH), Out of 49 patients with positive EGFR FISH test, 45 were treated with erlotinib. Median PFS in the intent-to-treat population was 3.3 months (95%CI: 1.8–3.9 months), and median overall survival was 7.9 months (95% CI: 5.1–12.6 months). Toxicity profile of erlotinib was consistent with its known safety profile. The trial was stopped prematurely at 63% of originally planned sample size due to accumulating evidence that EGFR gene copy number should not be used to select NSCLC patients to first-line therapy with EGFR TKI. Data on erlotinib efficacy according to EGFR , KRAS and BRAF mutations are additionally presented. Interpretation: This trial argues against using high gene copy number for selection of NSCLC patients to first-line therapy with EGFR TKIs. The study adds to the discussion on efficacy of other targeted agents in patients with target gene amplified tumors. |
| Databáze: | OpenAIRE |
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