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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/24021

Title: 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
Authors: Szutowicz-Zielinska, Ewa
Konopa, Krzysztof
Kowalczyk, Anna
Suszko-Kazarnowicz, Malgorzata
Duchnowska, Renata
Szczesna, Aleksandra
Ratajska, Magdalena
Sowa, Aleksander
Limon, Janusz
Biernat, Wojciech
Burzykowski, Tomasz
Jassem, Jacek
Dziadziuszko, Rafal
Issue Date: 2017
Citation: ONCOTARGET, 8(10), p. 17270-17278
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.
Notes: [Szutowicz-Zielinska, Ewa; Konopa, Krzysztof; Kowalczyk, Anna; Jassem, Jacek; Dziadziuszko, Rafal] Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. [Suszko-Kazarnowicz, Malgorzata] Ctr Pulm Dis Olsztyn, Dept Oncol, Olsztyn, Poland. [Duchnowska, Renata] Mil Inst Med, Dept Oncol, Warsaw, Poland. [Szczesna, Aleksandra] Mazovian Ctr Treatment Lung Dis & TB, Dept Lung Dis, Otwock, Poland. [Ratajska, Magdalena; Limon, Janusz] Med Univ Gdansk, Dept Biol & Genet, Gdansk, Poland. [Sowa, Aleksander] Roche, Warsaw, Poland. [Biernat, Wojciech] Dept Med Univ Gdansk, Gdansk, Poland. [Burzykowski, Tomasz] Hasselt Univ, Interuniv Inst Biostatist & Stat Bioinformat, Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/24021
DOI: 10.18632/oncotarget.13793
ISI #: 000396024600094
ISSN: 1949-2553
Category: A1
Type: Journal Contribution
Validation: ecoom, 2018
Appears in Collections: Research publications

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