Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

INTRODUCTION: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are mo...

Descripción completa

Detalles Bibliográficos
Autores principales: De Grève, Jacques, Van Meerbeeck, Jan, Vansteenkiste, Johan F., Decoster, Lore, Meert, Anne-Pascale, Vuylsteke, Peter, Focan, Christian, Canon, Jean-Luc, Humblet, Yves, Berchem, Guy, Colinet, Benoit, Galdermans, Danny, Bosquée, Lionel, Vermeij, Joanna, Dewaele, Alex, Geers, Caroline, Schallier, Denis, Teugels, Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816447/
https://www.ncbi.nlm.nih.gov/pubmed/27032107
http://dx.doi.org/10.1371/journal.pone.0147599
_version_ 1782424718160166912
author De Grève, Jacques
Van Meerbeeck, Jan
Vansteenkiste, Johan F.
Decoster, Lore
Meert, Anne-Pascale
Vuylsteke, Peter
Focan, Christian
Canon, Jean-Luc
Humblet, Yves
Berchem, Guy
Colinet, Benoit
Galdermans, Danny
Bosquée, Lionel
Vermeij, Joanna
Dewaele, Alex
Geers, Caroline
Schallier, Denis
Teugels, Erik
author_facet De Grève, Jacques
Van Meerbeeck, Jan
Vansteenkiste, Johan F.
Decoster, Lore
Meert, Anne-Pascale
Vuylsteke, Peter
Focan, Christian
Canon, Jean-Luc
Humblet, Yves
Berchem, Guy
Colinet, Benoit
Galdermans, Danny
Bosquée, Lionel
Vermeij, Joanna
Dewaele, Alex
Geers, Caroline
Schallier, Denis
Teugels, Erik
author_sort De Grève, Jacques
collection PubMed
description INTRODUCTION: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor. METHODS: Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease. RESULTS: Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung. CONCLUSION: The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339586
format Online
Article
Text
id pubmed-4816447
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-48164472016-04-14 Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT) De Grève, Jacques Van Meerbeeck, Jan Vansteenkiste, Johan F. Decoster, Lore Meert, Anne-Pascale Vuylsteke, Peter Focan, Christian Canon, Jean-Luc Humblet, Yves Berchem, Guy Colinet, Benoit Galdermans, Danny Bosquée, Lionel Vermeij, Joanna Dewaele, Alex Geers, Caroline Schallier, Denis Teugels, Erik PLoS One Research Article INTRODUCTION: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor. METHODS: Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease. RESULTS: Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung. CONCLUSION: The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339586 Public Library of Science 2016-03-31 /pmc/articles/PMC4816447/ /pubmed/27032107 http://dx.doi.org/10.1371/journal.pone.0147599 Text en © 2016 De Grève et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
De Grève, Jacques
Van Meerbeeck, Jan
Vansteenkiste, Johan F.
Decoster, Lore
Meert, Anne-Pascale
Vuylsteke, Peter
Focan, Christian
Canon, Jean-Luc
Humblet, Yves
Berchem, Guy
Colinet, Benoit
Galdermans, Danny
Bosquée, Lionel
Vermeij, Joanna
Dewaele, Alex
Geers, Caroline
Schallier, Denis
Teugels, Erik
Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)
title Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)
title_full Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)
title_fullStr Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)
title_full_unstemmed Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)
title_short Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)
title_sort prospective evaluation of first-line erlotinib in advanced non-small cell lung cancer (nsclc) carrying an activating egfr mutation: a multicenter academic phase ii study in caucasian patients (fielt)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816447/
https://www.ncbi.nlm.nih.gov/pubmed/27032107
http://dx.doi.org/10.1371/journal.pone.0147599
work_keys_str_mv AT degrevejacques prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT vanmeerbeeckjan prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT vansteenkistejohanf prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT decosterlore prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT meertannepascale prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT vuylstekepeter prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT focanchristian prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT canonjeanluc prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT humbletyves prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT berchemguy prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT colinetbenoit prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT galdermansdanny prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT bosqueelionel prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT vermeijjoanna prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT dewaelealex prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT geerscaroline prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT schallierdenis prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt
AT teugelserik prospectiveevaluationoffirstlineerlotinibinadvancednonsmallcelllungcancernsclccarryinganactivatingegfrmutationamulticenteracademicphaseiistudyincaucasianpatientsfielt