| Added by | llasorsa |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Ultra-sensitive EGFR T790M Detection as an Independent Prognostic Marker for Lung Cancer Patients Harboring EGFR del19 Mutations and Treated with First-generation TKIs |
| Creator | Vendrell et al. |
| Author | Julie A. Vendrell |
| Author | Romain Senal |
| Author | Isabelle Rouquette |
| Author | Xavier Quantin |
| Author | Jean-Louis Pujol |
| Author | Abdelali Bouidioua |
| Author | Sylvain Godreuil |
| Author | Etienne Coyaud |
| Author | Pierre Brousset |
| Author | Jérôme Solassol |
| Abstract | PURPOSE: The detection of preexisting EGFR T790M subclones and the assessment of their clinical significance in the pretreatment of patients with EGFR T790M non-small cell lung cancer (NSCLC) remain unclear. EXPERIMENTAL DESIGN: A total of 179 tumor samples from patients treated or not with a first-generation tyrosine kinase inhibitor (TKI) was analyzed. The presence of ultra-low levels of preexisting EGFRT790M mutation was evaluated using ultra-sensitive droplet digital PCR (ddPCR) and the clinical implication of these mutations on first-generation TKI efficiency assessed. RESULTS: With a ddPCR linear performance of 0.999 and an analytical sensitivity of approximately 0.001%, we observed a 66% (99/150) overall incidence of ultra-low EGFR T790M mutation. Among 82 patients harboring EGFR activating mutations, the presence of a preexisting EGFR T790M mutation prior to any treatment was significantly associated with a longer progression-free survival (PFS; P = 0.009; log-rank test). Interestingly, longer PFS was linked to concomitant EGFR del19 and ultra-low EGFR T790M mutations. Moreover, the presence of both EGFR del19 and ultra-low EGFR T790M mutations was identified as the best fit for predicting the clinical outcome of patients treated with TKI compared with an ultra-low EGFR T790M mutation status or an activating mutation alone (P = 0.042 and P = 0.0071, respectively). CONCLUSIONS: We demonstrate that the detection of the ultra-low EGFR T790M mutation in TKI-naïve patients is not a rare event. We suggest that ddPCR should be used in clinical practice to distinguish patients who may respond to first- or third-generation TKIs. |
| Publication | Clinical Cancer Research: An Official Journal of the American Association for Cancer Research |
| Volume | 25 |
| Issue | 14 |
| Pages | 4280-4289 |
| Date | 2019-07-15 |
| Journal Abbr | Clin Cancer Res |
| Language | eng |
| DOI | 10.1158/1078-0432.CCR-18-2683 |
| ISSN | 1557-3265 |
| Library Catalog | PubMed |
| Extra | PMID: 30936123 |
| Tags | Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung, Drug Resistance, Neoplasm, ErbB Receptors, Female, Humans, Lung Neoplasms, Male, Middle Aged, Molecular Targeted Therapy, Mutation, Prognosis, Progression-Free Survival, Protein Kinase Inhibitors |
| Date Added | 2022/09/29 - 15:08:55 |
| Date Modified | 2024/10/10 - 17:05:20 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
