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) - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Clinical Lung Cancer Année : 2019

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)

Résumé

IntroductionEvaluation 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.Materials and MethodsTumor 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.ResultsUsing 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.ConclusionsKRAS 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.

Domaines

Cancer
Fichier principal
Vignette du fichier
S152573041830336X.pdf (309.77 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02267702 , version 1 (22-10-2021)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Michèle Beau-Faller, Matthieu Texier, Hélène Blons, Nicolas Richard, Fabienne Escande, et al.. 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). Clinical Lung Cancer, 2019, 20 (3), pp.222-230. ⟨10.1016/j.cllc.2018.12.012⟩. ⟨hal-02267702⟩
126 Consultations
73 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More