Independent prognostic value of ultra-sensitive ...
Document type :
Article dans une revue scientifique: Article original
PMID :
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Title :
Independent prognostic value of ultra-sensitive quantification of tumor pre-treatment t790m subclones in egfr mutated non-small cell lung cancer (nsclc) treated by first/second generation tki, depends on variant allele frequency (vaf): results of the french cooperative thoracic intergroup (ifct) biomarkers france project
Author(s) :
Beau-Faller, Michele [Auteur]
Pencreach, Erwan [Auteur]
Leduc, Charlotte [Auteur]
Blons, Helene [Auteur]
Merlio, Jean-Philippe [Auteur]
Bringuier, Pierre-Paul [Auteur]
De Fraipont, Florence [Auteur]
Escande, Fabienne [Auteur]
Lemoine, Antoinette [Auteur]
Ouafik, L''''houcine [Auteur]
Denis, Marc [Auteur]
Hofman, Paul [Auteur]
Lacave, Roger [Auteur]
Melaabi, Samia [Auteur]
Langlais, Alexandra [Auteur]
Missy, Pascale [Auteur]
Morin, Franck [Auteur]
Moro-Sibilot, Denis [Auteur]
Barlesi, Fabrice [Auteur]
Cadranel, Jacques [Auteur]
Pencreach, Erwan [Auteur]
Leduc, Charlotte [Auteur]
Blons, Helene [Auteur]
Merlio, Jean-Philippe [Auteur]
Bringuier, Pierre-Paul [Auteur]
De Fraipont, Florence [Auteur]
Escande, Fabienne [Auteur]
Lemoine, Antoinette [Auteur]
Ouafik, L''''houcine [Auteur]
Denis, Marc [Auteur]
Hofman, Paul [Auteur]
Lacave, Roger [Auteur]
Melaabi, Samia [Auteur]
Langlais, Alexandra [Auteur]
Missy, Pascale [Auteur]
Morin, Franck [Auteur]
Moro-Sibilot, Denis [Auteur]
Barlesi, Fabrice [Auteur]
Cadranel, Jacques [Auteur]
Journal title :
Lung cancer (Amsterdam, Netherlands)
Abbreviated title :
Lung Cancer
Volume number :
140
Pages :
19-26
Publication date :
2019-11-15
ISSN :
1872-8332
Keyword(s) :
Droplet digital PCR (ddPCR)
T790M
EGFR mutation
Non-small cell lung cancer (NSCLC)
Variant allele frequency (VAF)
T790M
EGFR mutation
Non-small cell lung cancer (NSCLC)
Variant allele frequency (VAF)
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
T790M mutations inEGFR-mutated non-small cell lung cancer (NSCLC) account for nearly 50% of acquired resistance mechanisms to EGFR-TKIs. Earlier studies suggested that tumor T790M could also be detected in TKI-naïve ...
Show more >T790M mutations inEGFR-mutated non-small cell lung cancer (NSCLC) account for nearly 50% of acquired resistance mechanisms to EGFR-TKIs. Earlier studies suggested that tumor T790M could also be detected in TKI-naïve EGFR-mutated NSCLC. The aim of the study is to assess the prevalence and clinical significance of quantification of tumor pre-treatment T790M subclones. We analyzed 366 EGFR-mutated NSCLC patients of the real-life IFCT Biomarkers France study with available pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor DNA before treatment by first/second-generation EGFR-TKI. We used ultra-sensitive Droplet Digital Polymerase Chain Reaction (ddPCR) QX200 (BIO-RAD®, Hercules, CA, USA). All samples were tested in duplicate. ddPCR identified T790M in 19/240 specimens (8%). T790M-positive and T790M-negative populations were not different for clinical baseline characteristics. T790M Variant Allele Frequency (VAF) was > 0.01% <0.1%, > 0.1% <1%, > 1% <10%, and >10% in five (26.3%), six (31.6%), six (31.6%), and two (10.5%) patients, respectively. T790M VAF was >0.1% in 11/13 (84%) patients with rapid (<3 months) or usual progression (3-20 months) compared to 0/3 with low progression (>20 months) (p = 0.02). In a Cox model, T790M mutation positivity was correlated with overall survival (OS) and progression-free survival (PFS) for 10% > VAF >1% (hazard ratio [HR] = 2.83, 95% confidence interval [CI] 1.13-7.07, p = 0.03; HR=3.62, 95%CI 1.43-4.92, p = 0.007, respectively) and for VAF >10% (HR = 19.14, 95%CI 4.35-84.26, p < 0.001; HR = 17.89, 95%CI 2.21-144.86, p = 0.007, respectively). Ultra-sensitive detection of tumor T790M mutation concerned 8% of EGFR-mutated TKI-naïve NSCLC patients and has a negative prognostic value only for T790M VAF over 1%.Show less >
Show more >T790M mutations inEGFR-mutated non-small cell lung cancer (NSCLC) account for nearly 50% of acquired resistance mechanisms to EGFR-TKIs. Earlier studies suggested that tumor T790M could also be detected in TKI-naïve EGFR-mutated NSCLC. The aim of the study is to assess the prevalence and clinical significance of quantification of tumor pre-treatment T790M subclones. We analyzed 366 EGFR-mutated NSCLC patients of the real-life IFCT Biomarkers France study with available pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor DNA before treatment by first/second-generation EGFR-TKI. We used ultra-sensitive Droplet Digital Polymerase Chain Reaction (ddPCR) QX200 (BIO-RAD®, Hercules, CA, USA). All samples were tested in duplicate. ddPCR identified T790M in 19/240 specimens (8%). T790M-positive and T790M-negative populations were not different for clinical baseline characteristics. T790M Variant Allele Frequency (VAF) was > 0.01% <0.1%, > 0.1% <1%, > 1% <10%, and >10% in five (26.3%), six (31.6%), six (31.6%), and two (10.5%) patients, respectively. T790M VAF was >0.1% in 11/13 (84%) patients with rapid (<3 months) or usual progression (3-20 months) compared to 0/3 with low progression (>20 months) (p = 0.02). In a Cox model, T790M mutation positivity was correlated with overall survival (OS) and progression-free survival (PFS) for 10% > VAF >1% (hazard ratio [HR] = 2.83, 95% confidence interval [CI] 1.13-7.07, p = 0.03; HR=3.62, 95%CI 1.43-4.92, p = 0.007, respectively) and for VAF >10% (HR = 19.14, 95%CI 4.35-84.26, p < 0.001; HR = 17.89, 95%CI 2.21-144.86, p = 0.007, respectively). Ultra-sensitive detection of tumor T790M mutation concerned 8% of EGFR-mutated TKI-naïve NSCLC patients and has a negative prognostic value only for T790M VAF over 1%.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 :
2021-09-02T07:02:16Z