EGFR Amplification in Metastatic Colorectal Cancer.
Journal
Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089
Informations de publication
Date de publication:
02 11 2021
02 11 2021
Historique:
received:
14
12
2020
revised:
05
03
2021
accepted:
05
04
2021
pubmed:
8
4
2021
medline:
25
2
2022
entrez:
7
4
2021
Statut:
ppublish
Résumé
EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC. In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided. EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002). Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies.
Sections du résumé
BACKGROUND
EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC.
METHODS
In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided.
RESULTS
EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002).
CONCLUSION
Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies.
Identifiants
pubmed: 33825902
pii: 6213909
doi: 10.1093/jnci/djab069
pmc: PMC8562951
doi:
Substances chimiques
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1561-1569Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233736
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Références
Ann Oncol. 2018 Jan 1;29(1):44-70
pubmed: 29155929
BMC Genomics. 2012 Nov 04;13:591
pubmed: 23442169
Clin Cancer Res. 2020 Dec 15;26(24):6559-6567
pubmed: 32943459
J Clin Oncol. 2019 Nov 20;37(33):3099-3110
pubmed: 31539295
Clin Cancer Res. 2020 Mar 15;26(6):1395-1407
pubmed: 31852834
Ann Oncol. 2020 Nov;31(11):1491-1505
pubmed: 32853681
Nature. 2015 Oct 8;526(7572):263-7
pubmed: 26416732
Stat Med. 1989 May;8(5):551-61
pubmed: 2657958
Cancer Res. 2011 Dec 15;71(24):7587-96
pubmed: 22001862
Nat Commun. 2016 Dec 08;7:13665
pubmed: 27929064
J Natl Cancer Inst. 2005 May 4;97(9):643-55
pubmed: 15870435
JCO Precis Oncol. 2020 Nov 17;4:
pubmed: 33283138
Ann Oncol. 2008 Apr;19(4):717-23
pubmed: 17974556
Lifetime Data Anal. 1998;4(2):109-20
pubmed: 9658770
Mol Oncol. 2016 Mar;10(3):475-80
pubmed: 26774880
Clin Cancer Res. 2015 May 1;21(9):2157-66
pubmed: 25623215
JAMA Oncol. 2016 May 1;2(5):633-642
pubmed: 26867820
Gut. 2021 Sep;70(9):1632-1641
pubmed: 33199443
Ann Oncol. 2017 Dec 1;28(12):3009-3014
pubmed: 29045518
Cancer Cell. 2018 Jan 8;33(1):125-136.e3
pubmed: 29316426
JAMA Oncol. 2019 Sep 1;5(9):1268-1275
pubmed: 31268481
Lancet Oncol. 2020 Apr;21(4):497-507
pubmed: 32164906
Lancet Oncol. 2013 Jul;14(8):749-59
pubmed: 23725851
Clin Cancer Res. 2021 Jun 1;27(11):3126-3140
pubmed: 33542076
Ann Oncol. 2018 May 1;29(5):1108-1119
pubmed: 29659677