The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients.
EGFR TKIs
EGFR mutations
lung cancer
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
10 03 2019
10 03 2019
Historique:
received:
12
02
2019
revised:
28
02
2019
accepted:
05
03
2019
entrez:
13
3
2019
pubmed:
13
3
2019
medline:
13
3
2019
Statut:
epublish
Résumé
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:
Identifiants
pubmed: 30857358
pii: cancers11030341
doi: 10.3390/cancers11030341
pmc: PMC6468673
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Oncotarget. 2017 Feb 21;8(8):13611-13619
pubmed: 26799287
N Engl J Med. 2017 Jun 1;376(22):2109-2121
pubmed: 28445112
Curr Drug Targets. 2010 Jul;11(7):851-64
pubmed: 20388064
Ann Oncol. 2015 Aug;26(8):1710-4
pubmed: 25851630
Nat Commun. 2016 Jun 10;7:11815
pubmed: 27283993
Br J Cancer. 2014 May 27;110(11):2812-20
pubmed: 24743704
J Clin Oncol. 2012 Feb 1;30(4):433-40
pubmed: 22215752
Lung Cancer. 2017 Sep;111:23-29
pubmed: 28838393
Nat Rev Clin Oncol. 2014 Aug;11(8):473-81
pubmed: 24981256
Clin Cancer Res. 2017 May 1;23(9):2195-2202
pubmed: 27780855
Lung Cancer. 2016 May;95:94-7
pubmed: 27040858
J Thorac Oncol. 2013 Jul;8(7):e59-60
pubmed: 23774386
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2127-33
pubmed: 22773810
Sci Transl Med. 2015 Apr 15;7(283):283ra54
pubmed: 25877892
JAMA Oncol. 2018 May 1;4(5):739-742
pubmed: 29596544
Cancer Res. 2000 Jun 1;60(11):2906-11
pubmed: 10850436
Cancer Treat Rev. 2013 Aug;39(5):489-97
pubmed: 23022519
Cancer Res. 2001 Jun 1;61(11):4350-6
pubmed: 11389059
Br J Cancer. 1998 May;77(10):1568-72
pubmed: 9635830
Oncotarget. 2015 Jan 20;6(2):1315-26
pubmed: 25473901
BMC Cancer. 2015 Jan 31;15:26
pubmed: 25637035
Nat Med. 2016 Jan;22(1):105-13
pubmed: 26618723
Oncotarget. 2016 Jun 14;7(24):36311-36320
pubmed: 27121209
Ann Oncol. 2014 Feb;25(2):423-8
pubmed: 24478319
Clin Cancer Res. 2014 Apr 1;20(7):2001-10
pubmed: 24493829
Oncotarget. 2015 May 20;6(14):12783-95
pubmed: 25904052
Nat Med. 2015 Aug;21(8):846-53
pubmed: 26248267
Oncotarget. 2018 May 25;9(40):26195-26208
pubmed: 29899852
N Engl J Med. 2008 Jul 24;359(4):366-77
pubmed: 18596266
Br J Cancer. 2014 Nov 25;111(11):2203-4
pubmed: 25117816
Lung Cancer. 2015 Feb;87(2):204-6
pubmed: 25555368
J Pathol Transl Med. 2016 May;50(3):197-203
pubmed: 27086595