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- 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).
- Authors
Beau-Faller, Michèle; Texier, Matthieu; Blons, Hélène; Richard, Nicolas; Escande, Fabienne; Melaabi, Samia; Lizard, Sarab; De Fraipont, Florence; Longchampt, Elisabeth; Morin, Franck; Zalcman, Gérard; Pignon, Jean-Pierre; Cadranel, Jacques
- Abstract
<bold>Introduction: </bold>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.<bold>Materials and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
FRANCE; THERAPEUTIC use of antineoplastic agents; LUNG cancer; PROTEINS; RESEARCH; GENETIC mutation; RESEARCH methodology; LUNG tumors; CELL receptors; EVALUATION research; MEDICAL cooperation; TREATMENT effectiveness; TUMOR classification; COMPARATIVE studies; SURVIVAL analysis (Biometry); LONGITUDINAL method
- Publication
Clinical Lung Cancer, 2019, Vol 20, Issue 3, p222
- ISSN
1525-7304
- Publication type
journal article
- DOI
10.1016/j.cllc.2018.12.012