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

Author(s) :

Vendrell, Julie A. [Auteur]
Mazieres, Julien [Auteur]
Senal, Romain [Auteur]
Rouquette, Isabelle [Auteur]
Quantin, Xavier [Auteur]
Pujol, Jean-Louis [Auteur]
Roch, Benoit [Auteur]
Bouidioua, Abdelali [Auteur]
Godreuil, Sylvain [Auteur]
Coyaud, Etienne-Marie [Auteur]
Brousset, Pierre [Auteur]
Solassol, Jerome [Auteur]

Journal title :

Clinical cancer research . an official journal of the American Association for Cancer Research

Abbreviated title :

Clin. Cancer Res.

Volume number :

25

Pages :

-

Publication date :

2019-07-15

ISSN :

1078-0432

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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 EGFR(T790M) 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-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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:57:40Z