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Different EGFR Gene Mutations in Exon 18, 19 and 21 as Prognostic and Predictive Markers in NSCLC: A Single Institution Analysis

Molecular Diagnosis & Therapy volume 20, pages 55–63 (2016)Cite this article

Abstract

Background

Mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) predict longer overall survival (OS) and response to EGFR tyrosine kinase inhibitors (TKIs). The clinical relevance of different mutations in terms of response to TKIs and prognosis is still unclear.

Objectives

The aims of the present study were to assess the relationship between mutations in exon 18, 19 and 21 in patients treated with TKIs and their clinical outcomes, and evaluate the role of specific point mutations.

Methods

We included in this analysis 55 patients with metastatic NSCLC and mutations in exon 18, 19 and 21, treated in our center between 2004 and 2014. All patients received treatment with TKIs in first and/or subsequent lines. Endpoints analyzed were OS (primary) and time to progression (TTP) (secondary), according to exon mutations and specific point mutations.

Results

A strong negative prognostic association for OS (p = 0.02) and TTP (p = 0.03) was found for exon 18 mutations compared with exon 19 deletions . A trend toward a longer median OS was observed in exon 19 deletions versus exon 21 point mutations (+6.6 months), although more exon 19-mutated patients had brain metastases at diagnosis. Comparing each mutation, p.E746_A750del and p.E746_T751del of exon 19 and p.L858R mutation of exon 21, a trend toward improved OS in p.E746_A750del was found.

Conclusion

In this analysis, exon 19 deletions were associated with better outcomes, despite a higher percentage of brain metastases in this group. The prognostic relevance of p.E746_A750del requires further studies.

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Acknowledgments

All the authors contributed to the article, without any external involvement.

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Affiliations

  1. Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy

    Sabrina Rossi, Ettore D’Argento, Michele Basso, Antonia Strippoli, Vincenzo Dadduzio, Eleonora Cerchiaro, Alessandra Cassano & Carlo Barone

  2. Department of Pathology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy

    Maurizio Martini

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  1. Sabrina Rossi
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  2. Ettore D’Argento
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Correspondence to Sabrina Rossi.

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Conflicts of interest

Sabrina Rossi, Ettore D’Argento, Michele Basso, Antonia Strippoli, Vincenzo Dadduzio, Eleonora Cerchiaro, Maurizio Martini, Alessandra Cassano and Carlo Barone have no conflicts of interest that are directly relevant to the content of this article.

Funding

Sabrina Rossi, Ettore D’Argento, Michele Basso, Antonia Strippoli, Vincenzo Dadduzio, Eleonora Cerchiaro, Maurizio Martini, Alessandra Cassano and Carlo Barone have received no funding for the conduct of this study.

Ethical approval and informed consent

The study has been conducted in accordance with the rules of the local Ethics Committee and the Declaration of Helsinki. All patients provided a written consent for use of their clinical data; a separate consent for molecular analyses was obtained.

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Rossi, S., D’Argento, E., Basso, M. et al. Different EGFR Gene Mutations in Exon 18, 19 and 21 as Prognostic and Predictive Markers in NSCLC: A Single Institution Analysis. Mol Diagn Ther 20, 55–63 (2016). https://doi.org/10.1007/s40291-015-0176-x

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  • DOI: https://doi.org/10.1007/s40291-015-0176-x

Keywords

  • Overall Survival
  • Epidermal Growth Factor Receptor
  • Brain Metastasis
  • Gefitinib
  • Erlotinib