Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate...

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Autores: Morán, Teresa, Felip, Eudald|||0000-0002-3812-1313, Bosch-Barrera, J.|||0000-0002-0893-7821, de Aguirre, Itziar, Ramirez, Jose Luis, Mesia, Carles, Carcereny, Enric|||0000-0001-5235-5602, Roa, Diana, Sais, Elia, García García, Yolanda|||0000-0002-0280-4382, Blanco, Remei|||0000-0001-6748-0326, Sanchez, Silvia, Villacorta, Claudia Rosa, Queralt, C.|||0000-0001-9875-0173, Velarde, Jose María, Rosell, Rafael|||0000-0003-0817-3400
Formato: artículo
Fecha de publicación:2018
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:238826
Acesso em linha:https://ddd.uab.cat/record/238826
https://dx.doi.org/urn:doi:10.18632/oncotarget.25478
Access Level:acceso abierto
Palavra-chave:EGFR-T790M mutation
Serum/plasma
Osimertinib
Acquired resistance
EGFR tyrosine kinase inhibitors
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spelling Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancerMorán, TeresaFelip, Eudald|||0000-0002-3812-1313Bosch-Barrera, J.|||0000-0002-0893-7821de Aguirre, ItziarRamirez, Jose LuisMesia, CarlesCarcereny, Enric|||0000-0001-5235-5602Roa, DianaSais, EliaGarcía García, Yolanda|||0000-0002-0280-4382Blanco, Remei|||0000-0001-6748-0326Sanchez, SilviaVillacorta, Claudia RosaQueralt, C.|||0000-0001-9875-0173Velarde, Jose MaríaRosell, Rafael|||0000-0003-0817-3400EGFR-T790M mutationSerum/plasmaOsimertinibAcquired resistanceEGFR tyrosine kinase inhibitorsOsimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance.Universitat Autònoma de Barcelona 22018-01-0120182018-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/238826https://dx.doi.org/urn:doi:10.18632/oncotarget.25478reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2388262026-06-06T12:50:31Z
dc.title.none.fl_str_mv Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
title Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
spellingShingle Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
Morán, Teresa
EGFR-T790M mutation
Serum/plasma
Osimertinib
Acquired resistance
EGFR tyrosine kinase inhibitors
title_short Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
title_full Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
title_fullStr Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
title_full_unstemmed Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
title_sort Monitoring EGFR -T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
dc.creator.none.fl_str_mv Morán, Teresa
Felip, Eudald|||0000-0002-3812-1313
Bosch-Barrera, J.|||0000-0002-0893-7821
de Aguirre, Itziar
Ramirez, Jose Luis
Mesia, Carles
Carcereny, Enric|||0000-0001-5235-5602
Roa, Diana
Sais, Elia
García García, Yolanda|||0000-0002-0280-4382
Blanco, Remei|||0000-0001-6748-0326
Sanchez, Silvia
Villacorta, Claudia Rosa
Queralt, C.|||0000-0001-9875-0173
Velarde, Jose María
Rosell, Rafael|||0000-0003-0817-3400
author Morán, Teresa
author_facet Morán, Teresa
Felip, Eudald|||0000-0002-3812-1313
Bosch-Barrera, J.|||0000-0002-0893-7821
de Aguirre, Itziar
Ramirez, Jose Luis
Mesia, Carles
Carcereny, Enric|||0000-0001-5235-5602
Roa, Diana
Sais, Elia
García García, Yolanda|||0000-0002-0280-4382
Blanco, Remei|||0000-0001-6748-0326
Sanchez, Silvia
Villacorta, Claudia Rosa
Queralt, C.|||0000-0001-9875-0173
Velarde, Jose María
Rosell, Rafael|||0000-0003-0817-3400
author_role author
author2 Felip, Eudald|||0000-0002-3812-1313
Bosch-Barrera, J.|||0000-0002-0893-7821
de Aguirre, Itziar
Ramirez, Jose Luis
Mesia, Carles
Carcereny, Enric|||0000-0001-5235-5602
Roa, Diana
Sais, Elia
García García, Yolanda|||0000-0002-0280-4382
Blanco, Remei|||0000-0001-6748-0326
Sanchez, Silvia
Villacorta, Claudia Rosa
Queralt, C.|||0000-0001-9875-0173
Velarde, Jose María
Rosell, Rafael|||0000-0003-0817-3400
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv EGFR-T790M mutation
Serum/plasma
Osimertinib
Acquired resistance
EGFR tyrosine kinase inhibitors
topic EGFR-T790M mutation
Serum/plasma
Osimertinib
Acquired resistance
EGFR tyrosine kinase inhibitors
description Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance.
publishDate 2018
dc.date.none.fl_str_mv 2
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/238826
https://dx.doi.org/urn:doi:10.18632/oncotarget.25478
url https://ddd.uab.cat/record/238826
https://dx.doi.org/urn:doi:10.18632/oncotarget.25478
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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