Clinical relevance of egfr- or kras-mutated ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
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)
Author(s) :
Beau-Faller, Michele [Auteur]
Texier, Matthieu [Auteur]
Blons, Helene [Auteur]
Richard, Nicolas [Auteur]
Escande, Fabienne [Auteur]
Melaabi, Samia [Auteur]
Lizard, Sarab [Auteur]
De Fraipont, Florence [Auteur]
Longchampt, Elisabeth [Auteur]
Morin, Franck [Auteur]
Zalcman, Gerard [Auteur]
Pignon, Jean-Pierre [Auteur]
Cadranel, Jacques [Auteur]
Texier, Matthieu [Auteur]
Blons, Helene [Auteur]
Richard, Nicolas [Auteur]
Escande, Fabienne [Auteur]
Melaabi, Samia [Auteur]
Lizard, Sarab [Auteur]
De Fraipont, Florence [Auteur]
Longchampt, Elisabeth [Auteur]
Morin, Franck [Auteur]
Zalcman, Gerard [Auteur]
Pignon, Jean-Pierre [Auteur]
Cadranel, Jacques [Auteur]
Journal title :
Clinical lung cancer
Abbreviated title :
Clin Lung Cancer
Publication date :
2018-12-19
ISSN :
1938-0690
Keyword(s) :
NSCLC
Sensitivity
Driver mutations
Molecular techniques
Tyrosine kinase inhibitor
Sensitivity
Driver mutations
Molecular techniques
Tyrosine kinase inhibitor
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Submission date :
2021-09-02T07:02:02Z