Monitoring Therapeutic Response and Resistance: Analysis of Circulating Tumor DNA in Patients With ALK+ Lung Cancer.
Adult
Aged
Aged, 80 and over
Anaplastic Lymphoma Kinase
/ biosynthesis
Carcinoma, Non-Small-Cell Lung
/ blood
Circulating Tumor DNA
/ blood
Drug Resistance, Neoplasm
Female
Humans
Lung Neoplasms
/ blood
Male
Middle Aged
Mutation
Oncogene Proteins, Fusion
/ genetics
Piperazines
/ therapeutic use
Prognosis
Protein Kinase Inhibitors
/ therapeutic use
Pyridazines
/ therapeutic use
ALK receptor tyrosine kinase
Circulating tumor DNA
Liquid biopsies
NSCLC
Next-generation sequencing
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
31
03
2019
revised:
01
08
2019
accepted:
01
08
2019
pubmed:
26
8
2019
medline:
26
8
2020
entrez:
26
8
2019
Statut:
ppublish
Résumé
Despite initial effectiveness of ALK receptor tyrosine kinase inhibitors (TKIs) in patients with ALK+ NSCLC, therapeutic resistance will ultimately develop. Serial tracking of genetic alterations detected in circulating tumor DNA (ctDNA) can be an informative strategy to identify response and resistance. This study evaluated the utility of analyzing ctDNA as a function of response to ensartinib, a potent second-generation ALK TKI. Pre-treatment plasma was collected from 76 patients with ALK+ NSCLC who were ALK TKI-naive or had received prior ALK TKI, and analyzed for specific genetic alterations. Longitudinal plasma samples were analyzed from a subset (n = 11) of patients. Analysis of pre-treatment tumor biopsy specimens from 22 patients was compared with plasma. Disease-associated genetic alterations were detected in 74% (56 of 76) of patients, the most common being EML4-ALK. Concordance of ALK fusion between plasma and tissue was 91% (20 of 22 blood and tissue samples). Twenty-four ALK kinase domain mutations were detected in 15 patients, all had previously received an ALK TKI; G1269A was the most prevalent (4 of 24). Patients with a detectable EML4-ALK variant 1 (V1) fusion had improved response (9 of 17 patients; 53%) to ensartinib compared to patients with EML4-ALK V3 fusion (one of seven patients; 14%). Serial changes in ALK alterations were observed during therapy. Clinical utility of ctDNA was shown, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients who may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs.
Identifiants
pubmed: 31446141
pii: S1556-0864(19)30665-3
doi: 10.1016/j.jtho.2019.08.003
pmc: PMC6823161
mid: NIHMS1538167
pii:
doi:
Substances chimiques
Circulating Tumor DNA
0
EML4-ALK fusion protein, human
0
Oncogene Proteins, Fusion
0
Piperazines
0
Protein Kinase Inhibitors
0
Pyridazines
0
ALK protein, human
EC 2.7.10.1
Anaplastic Lymphoma Kinase
EC 2.7.10.1
ensartinib
SMA5ZS5B22
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1901-1911Subventions
Organisme : Damon Runyon Cancer Research Foundation
ID : CI-65-13
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA090625
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA129243
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA121210
Pays : United States
Informations de copyright
Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Références
Cancer Discov. 2016 Oct;6(10):1084-1086
pubmed: 27698100
Clin Cancer Res. 2016 Feb 15;22(4):915-22
pubmed: 26459174
Neoplasia. 2008 Mar;10(3):298-302
pubmed: 18320074
J Thorac Oncol. 2015 May;10(5):768-777
pubmed: 25738220
Clin Cancer Res. 2016 Dec 15;22(24):6010-6020
pubmed: 27281561
Chem Biol Drug Des. 2011 Dec;78(6):999-1005
pubmed: 22034911
J Cancer Res Clin Oncol. 2016 Apr;142(4):833-43
pubmed: 26646246
Cancer Res. 2011 Jul 15;71(14):4920-31
pubmed: 21613408
J Clin Oncol. 2016 Oct 1;34(28):3383-9
pubmed: 27354483
J Clin Oncol. 2017 Aug 1;35(22):2490-2498
pubmed: 28475456
Clin Cancer Res. 2017 Sep 1;23(17):5101-5111
pubmed: 28539465
Lancet. 2017 Mar 4;389(10072):917-929
pubmed: 28126333
Hum Pathol. 2009 Aug;40(8):1152-8
pubmed: 19386350
J Thorac Oncol. 2015 Jul;10(7):e55-7
pubmed: 26134233
N Engl J Med. 2017 Aug 31;377(9):829-838
pubmed: 28586279
Clin Cancer Res. 2018 Jun 15;24(12):2758-2770
pubmed: 29599410
J Thorac Oncol. 2018 Jan;13(1):112-123
pubmed: 28951314
Lancet Oncol. 2017 Dec;18(12):1590-1599
pubmed: 29074098
JAMA. 2014 May 21;311(19):1998-2006
pubmed: 24846037
Jpn J Clin Oncol. 2018 Apr 1;48(4):367-375
pubmed: 29474558
J Clin Oncol. 2018 Apr 20;36(12):1199-1206
pubmed: 29373100
Clin Cancer Res. 2018 Jun 15;24(12):2771-2779
pubmed: 29563138
N Engl J Med. 2013 Jun 20;368(25):2385-94
pubmed: 23724913
Oncotarget. 2016 Oct 4;7(40):65208-65217
pubmed: 27564104
Cancer Discov. 2016 Oct;6(10):1118-1133
pubmed: 27432227
PLoS One. 2017 Apr 27;12(4):e0176241
pubmed: 28448587
JCO Precis Oncol. 2018;2018:null
pubmed: 29376144
Clin Cancer Res. 2018 Jul 15;24(14):3334-3347
pubmed: 29636358
Clin Cancer Res. 2016 Dec 1;22(23):5772-5782
pubmed: 27601595
Mol Cell Oncol. 2015 Apr 01;2(3):e985549
pubmed: 27308463
J Thorac Oncol. 2014 Mar;9(3):e27-8
pubmed: 24518097