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Ann Oncol. 2014 Jan;25(1):126-31. doi: 10.1093/annonc/mdt418. Epub 2013 Nov 26.

Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network.

Author information

1
Department of Biochemistry and Molecular Biology, Strasbourg University Hospital, Strasbourg.

Abstract

BACKGROUND:

There is scarce data available about epidermal growth factor receptor (EGFR) mutations other than common exon 19 deletions and exon 21 (L858R) mutations.

PATIENTS AND METHODS:

EGFR exon 18 and/or exon 20 mutations were collected from 10 117 non-small-cell lung cancer (NSCLC) samples analysed at 15 French National Cancer Institute (INCa)-platforms of the ERMETIC-IFCT network.

RESULTS:

Between 2008 and 2011, 1047 (10%) samples were EGFR-mutated, 102 (10%) with rare mutations: 41 (4%) in exon 18, 49 (5%) in exon 20, and 12 (1%) with other EGFR mutations. Exon 20 mutations were related to never-smoker status, when compared with exon 18 mutations (P < 0.001). Median overall survival (OS) of metastatic disease was 21 months [95% confidence interval (CI) 12-24], worse in smokers than in non-smoker patients with exon 20 mutations (12 versus 21 months; hazard ratio [HR] for death 0.27, 95% CI 0.08-0.87, P = 0.03). Under EGFR-tyrosine kinase inhibitors (TKIs), median OS was 14 months (95% CI 6-21); disease control rate was better for complex mutations (6 of 7, 86%) than for single mutations (16 of 40, 40%) (P = 0.03).

CONCLUSIONS:

Rare EGFR-mutated NSCLCs are heterogeneous, with resistance of distal exon 20 insertions and better sensitivity of exon 18 or complex mutations to EGFR-TKIs, probably requiring individual assessment.

KEYWORDS:

epidermal growth factor receptor mutations; exon 18 mutations; exon 20 mutations; non-small-cell lung cancer; tyrosine-kinase inhibitors

PMID:
24285021
PMCID:
PMC3868323
DOI:
10.1093/annonc/mdt418
[Indexed for MEDLINE]
Free PMC Article

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