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Oncotarget. 2017 Mar 7;8(10):17270-17278. doi: 10.18632/oncotarget.13793.

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.

Author information

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, Warszawa, Poland.
7
Department of Pathomorphology, Medical University of Gdańsk, Poland.
8
Interuniversity Institute of Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium.

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.

KEYWORDS:

epidermal growth factor receptor; erlotinib; gene copy number; non-small cell lung cancer

PMID:
27924059
PMCID:
PMC5370039
DOI:
10.18632/oncotarget.13793
[Indexed for MEDLINE]
Free PMC Article

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