| Added by | pcoopman |
|---|---|
| Group name | EquipePC |
| Item Type | Journal Article |
| Title | Ultra-sensitive EGFRT790Mdetection as an independent prognostic marker for lung cancer patients harboring EGFRdel19mutations and treated with first-generation TKIs |
| Creator | Vendrell et al. |
| Author | Julie 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 |
| Abstract | PURPOSE: The detection of pre-existing EGFRT790M subclones and the assessment of their clinical significance in the pretreatment of EGFRT790M non-small cell lung cancer (NSCLC) patients 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 pre-existing 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 EGFRT790M mutation. Among 82 patients harboring EGFRactivating mutations, the presence of a pre-existing EGFRT790M mutation prior to any treatment was significantly associated with a longer PFS (P = 0.009; Log-rank test). Interestingly, longer PFS was linked to concomitant EGFRdel19 and ultra-low EGFRT790M mutations. Moreover, the presence of both EGFRdel19 and ultra-low EGFRT790M mutations was identified as the best fit for predicting the clinical outcome of patients treated with TKI compared with an ultra-low EGFRT790M 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 EGFRT790M mutation in TKI-naive 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 |
| Date | Apr 01, 2019 |
| Journal Abbr | Clin. Cancer Res. |
| Language | eng |
| DOI | 10.1158/1078-0432.CCR-18-2683 |
| ISSN | 1078-0432 |
| Library Catalog | PubMed |
| Extra | PMID: 30936123 |
| Tags | clinic, first-last-corresponding |
| Date Added | 2019/05/16 - 12:04:42 |
| Date Modified | 2023/11/15 - 16:37:54 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
