Clinical Relevance of EGFR- or KRAS-mutated Subclones in Patients With Advanced Non-small-cell Lung Cancer Receiving Erlotinib in a French Prospective Cohort (IFCT ERMETIC2 Cohort - Part 2).
Aged
Antineoplastic Agents
/ therapeutic use
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cohort Studies
ErbB Receptors
/ genetics
Erlotinib Hydrochloride
/ therapeutic use
Female
France
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Mutation
/ genetics
Neoplasm Staging
Prospective Studies
Proto-Oncogene Proteins p21(ras)
/ genetics
Survival Analysis
Treatment Outcome
Driver mutations
Molecular techniques
NSCLC
Sensitivity
Tyrosine kinase inhibitor
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
22
08
2018
revised:
03
12
2018
accepted:
11
12
2018
pubmed:
27
1
2019
medline:
4
4
2020
entrez:
26
1
2019
Statut:
ppublish
Résumé
Evaluation of EGFR Mutation status for the administration of EGFR-TKIs in non-small cell lung Carcinoma (ERMETIC) was a prospective study designed to validate the prognostic value of EGFR/KRAS mutations in patients with advanced non-small-cell lung cancer (NSCLC), all receiving a first-generation tyrosine kinase inhibitor, erlotinib. ERMETIC2 was an ancillary project evaluating the clinical value of common EGFR/KRAS-mutated subclones regarding prognosis using highly sensitive molecular detection methods. Tumor samples from 228 patients with NSCLC (59% adenocarcinoma, 37% women, and 19% never/former smokers) were available for reanalysis using alternative highly sensitive molecular techniques. A multivariate Cox model was used for prognostic analysis. Using alternative highly sensitive techniques, 16 EGFR and 51 KRAS supplementary mutations were newly identified, all still exclusive, leading to an overall rate of 12.3% (n = 28) and 33.3% (n = 76), respectively. Using real-time polymerase chain reaction (hybridization probe), they were significantly associated with progression-free survival (P = .02) and overall survival (OS) (P = .01), which were better for EGFR-mutated patients for progression-free survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.28-0.78) and OS (HR, 0.56; 95% CI, 0.31-1), and worse for KRAS mutations and OS (HR, 1.63; 95% CI, 1.09-2.44). Using the most sensitive technique detection for KRAS-clamp polymerase chain reaction-KRAS mutated subclones did not impact OS. KRAS and EGFR mutations were detected in higher proportions by alternative highly sensitive molecular techniques compared with direct Sanger sequencing. However, minor KRAS-mutated subclones offered no prognostic value when representing less than 1% of the tumor cells.
Identifiants
pubmed: 30679079
pii: S1525-7304(18)30336-X
doi: 10.1016/j.cllc.2018.12.012
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
KRAS protein, human
0
Erlotinib Hydrochloride
DA87705X9K
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
222-230Informations de copyright
Copyright © 2018. Published by Elsevier Inc.