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The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients

Recent findings suggest that a fraction of EGFR-mutant non-small-cell lung cancers (NSCLC) carry additional driver mutations that could potentially affect the activity of EGFR tyrosine kinase inhibitors (TKIs). We investigated the role of concomitant KRAS, NRAS, BRAF, PIK3CA, MET and ERBB2 mutations...

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Autores principales: Rachiglio, Anna Maria, Fenizia, Francesca, Piccirillo, Maria Carmela, Galetta, Domenico, Crinò, Lucio, Vincenzi, Bruno, Barletta, Emiddio, Pinto, Carmine, Ferraù, Francesco, Lambiase, Matilde, Montanino, Agnese, Roma, Cristin, Ludovini, Vienna, Montagna, Elisabetta Sara, De Luca, Antonella, Rocco, Gaetano, Botti, Gerardo, Perrone, Francesco, Morabito, Alessandro, Normanno, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468673/
https://www.ncbi.nlm.nih.gov/pubmed/30857358
http://dx.doi.org/10.3390/cancers11030341
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author Rachiglio, Anna Maria
Fenizia, Francesca
Piccirillo, Maria Carmela
Galetta, Domenico
Crinò, Lucio
Vincenzi, Bruno
Barletta, Emiddio
Pinto, Carmine
Ferraù, Francesco
Lambiase, Matilde
Montanino, Agnese
Roma, Cristin
Ludovini, Vienna
Montagna, Elisabetta Sara
De Luca, Antonella
Rocco, Gaetano
Botti, Gerardo
Perrone, Francesco
Morabito, Alessandro
Normanno, Nicola
author_facet Rachiglio, Anna Maria
Fenizia, Francesca
Piccirillo, Maria Carmela
Galetta, Domenico
Crinò, Lucio
Vincenzi, Bruno
Barletta, Emiddio
Pinto, Carmine
Ferraù, Francesco
Lambiase, Matilde
Montanino, Agnese
Roma, Cristin
Ludovini, Vienna
Montagna, Elisabetta Sara
De Luca, Antonella
Rocco, Gaetano
Botti, Gerardo
Perrone, Francesco
Morabito, Alessandro
Normanno, Nicola
author_sort Rachiglio, Anna Maria
collection PubMed
description Recent findings suggest that a fraction of EGFR-mutant non-small-cell lung cancers (NSCLC) carry additional driver mutations that could potentially affect the activity of EGFR tyrosine kinase inhibitors (TKIs). We investigated the role of concomitant KRAS, NRAS, BRAF, PIK3CA, MET and ERBB2 mutations (other mutations) on the outcome of 133 EGFR mutant patients, who received first-line therapy with EGFR TKIs between June 2008 and December 2014. Analysis of genomic DNA by Next Generation Sequencing (NGS) revealed the presence of hotspot mutations in genes other than the EGFR, including KRAS, NRAS, BRAF, ERBB2, PIK3CA, or MET, in 29/133 cases (21.8%). A p.T790M mutation was found in 9/133 tumour samples (6.8%). The progression free survival (PFS) of patients without other mutations was 11.3 months vs. 7 months in patients with other mutations (log-rank test univariate: p = 0.047). In a multivariate Cox regression model including the presence of other mutations, age, performance status, smoking status, and the presence of p.T790M mutations, the presence of other mutations was the only factor significantly associated with PFS (Hazard Ratio 1.63, 95% CI 1.04–2.58; p = 0.035). In contrast, no correlation was found between TP53 mutations and patients’ outcome. These data suggest that a subgroup of EGFR mutant tumours have concomitant driver mutations that might affect the activity of first-line EGFR TKIs.
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spelling pubmed-64686732019-04-24 The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients Rachiglio, Anna Maria Fenizia, Francesca Piccirillo, Maria Carmela Galetta, Domenico Crinò, Lucio Vincenzi, Bruno Barletta, Emiddio Pinto, Carmine Ferraù, Francesco Lambiase, Matilde Montanino, Agnese Roma, Cristin Ludovini, Vienna Montagna, Elisabetta Sara De Luca, Antonella Rocco, Gaetano Botti, Gerardo Perrone, Francesco Morabito, Alessandro Normanno, Nicola Cancers (Basel) Article Recent findings suggest that a fraction of EGFR-mutant non-small-cell lung cancers (NSCLC) carry additional driver mutations that could potentially affect the activity of EGFR tyrosine kinase inhibitors (TKIs). We investigated the role of concomitant KRAS, NRAS, BRAF, PIK3CA, MET and ERBB2 mutations (other mutations) on the outcome of 133 EGFR mutant patients, who received first-line therapy with EGFR TKIs between June 2008 and December 2014. Analysis of genomic DNA by Next Generation Sequencing (NGS) revealed the presence of hotspot mutations in genes other than the EGFR, including KRAS, NRAS, BRAF, ERBB2, PIK3CA, or MET, in 29/133 cases (21.8%). A p.T790M mutation was found in 9/133 tumour samples (6.8%). The progression free survival (PFS) of patients without other mutations was 11.3 months vs. 7 months in patients with other mutations (log-rank test univariate: p = 0.047). In a multivariate Cox regression model including the presence of other mutations, age, performance status, smoking status, and the presence of p.T790M mutations, the presence of other mutations was the only factor significantly associated with PFS (Hazard Ratio 1.63, 95% CI 1.04–2.58; p = 0.035). In contrast, no correlation was found between TP53 mutations and patients’ outcome. These data suggest that a subgroup of EGFR mutant tumours have concomitant driver mutations that might affect the activity of first-line EGFR TKIs. MDPI 2019-03-10 /pmc/articles/PMC6468673/ /pubmed/30857358 http://dx.doi.org/10.3390/cancers11030341 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rachiglio, Anna Maria
Fenizia, Francesca
Piccirillo, Maria Carmela
Galetta, Domenico
Crinò, Lucio
Vincenzi, Bruno
Barletta, Emiddio
Pinto, Carmine
Ferraù, Francesco
Lambiase, Matilde
Montanino, Agnese
Roma, Cristin
Ludovini, Vienna
Montagna, Elisabetta Sara
De Luca, Antonella
Rocco, Gaetano
Botti, Gerardo
Perrone, Francesco
Morabito, Alessandro
Normanno, Nicola
The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
title The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
title_full The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
title_fullStr The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
title_full_unstemmed The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
title_short The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
title_sort presence of concomitant mutations affects the activity of egfr tyrosine kinase inhibitors in egfr-mutant non-small cell lung cancer (nsclc) patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468673/
https://www.ncbi.nlm.nih.gov/pubmed/30857358
http://dx.doi.org/10.3390/cancers11030341
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