Clinical Research Papers:
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
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Ewa Szutowicz-Zielińska1,*, Krzysztof Konopa1,*, Anna Kowalczyk1, Małgorzata Suszko-Każarnowicz2, Renata Duchnowska3, Aleksandra Szczęsna4, Magdalena Ratajska5, Aleksander Sowa6, Janusz Limon5, Wojciech Biernat7, Tomasz Burzykowski8, Jacek Jassem1 and Rafał Dziadziuszko1
1 Department of Oncology and Radiotherapy, Medical University of Gdańsk, 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 Gdańsk, Poland
6 Roche, Poland
7 Department of Pathomorphology, Medical University of Gdańsk, Poland
8 Interuniversity Institute of Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium
* Ewa Szutowicz-Zielinska and Krzysztof Konopa contributed equally to this study
Ewa Szutowicz-Zielińska, 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
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.
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