Circulating free tumor-derived DNA to detect EGFR mutations in patients with advanced NSCLC: French subset analysis of the ASSESS study

Marc G. Denis, Marie Pierre Lafourcade, Gwenaëlle Le Garff, Charles Dayen, Lionel Falchero, Pascal Thomas, Chrystèle Locher, Gérard Oliviero, Muriel Licour, Martin Reck, Nicola Normanno, Olivier Molinier

Research output: Contribution to journalArticle

Abstract

Background: The non-interventional ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for epidermal growth factor receptor (EGFR) mutation testing in patients with advanced non-small-cell lung cancer (NSCLC), in a real-world setting across 56 centers in Europe and Japan. The high mutation status concordance between 1162 matched tissue/cytology and plasma samples (89%, sensitivity =46%, specificity =97%) suggested that ctDNA is a feasible sample for EGFR mutation analysis. We report data for the French subset of patients (pre-planned analysis). Methods: Eligible patients (stage IIIA/B/IV locally advanced/metastatic treatment-naive advanced NSCLC) provided diagnostic tissue/cytology and plasma samples. DNA extracted from tissue/cytology samples was subjected to EGFR mutation testing as per local practice; a designated laboratory performed ctDNA extraction/mutation testing of plasma samples. The primary outcome was EGFR mutation status concordance between matched tumor and plasma samples. Results: Of the 1,311 patients enrolled in the ASSESS trial, 145 were recruited from 9 centers in France. Tumor samples from 130 patients were collected and 126 were evaluable for EGFR mutation analysis. Activating EGFR mutations were identified in 13 of the 126 patient tumor samples (EGFR mutation frequency 10.3%). For plasma testing, 10 of the 145 samples tested were positive for EGFR mutations (EGFR mutation frequency 6.9%). EGFR mutation rate was significantly higher in never- versus ever-smokers (stepwise logistic regression: tumor, P<0.0001; plasma, P=0.0008). Mutation status concordance between 126 matched patient samples was 96.0% [121/126; 95% confidence intervals (CI), 91.0–98.7]. Of the 113 EGFR mutation-negative patient tissue samples, one tested plasma-positive; reanalysis of plasma via two different techniques confirmed the presence of a L858R mutation, indicating a tissue false-negative result. Based on these data, sensitivity of plasma testing was 64.3% (9/14; 95% CI, 35.1–87.2%) and its specificity was 100.0% (112/112; 95% CI, 96.8–100.0%).

Original languageEnglish
Pages (from-to)1370-1378
Number of pages9
JournalJournal of Thoracic Disease
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Mutation
DNA
Neoplasms
Mutation Rate
Cell Biology
Confidence Intervals
France
Japan
Logistic Models
Sensitivity and Specificity

Keywords

  • Circulating tumor DNA
  • Epidermal growth factor receptor (EGFR)
  • Non-small cell lung cancer (NSCLC)
  • Plasma

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Circulating free tumor-derived DNA to detect EGFR mutations in patients with advanced NSCLC : French subset analysis of the ASSESS study. / Denis, Marc G.; Lafourcade, Marie Pierre; Le Garff, Gwenaëlle; Dayen, Charles; Falchero, Lionel; Thomas, Pascal; Locher, Chrystèle; Oliviero, Gérard; Licour, Muriel; Reck, Martin; Normanno, Nicola; Molinier, Olivier.

In: Journal of Thoracic Disease, Vol. 11, No. 4, 01.04.2019, p. 1370-1378.

Research output: Contribution to journalArticle

Denis, MG, Lafourcade, MP, Le Garff, G, Dayen, C, Falchero, L, Thomas, P, Locher, C, Oliviero, G, Licour, M, Reck, M, Normanno, N & Molinier, O 2019, 'Circulating free tumor-derived DNA to detect EGFR mutations in patients with advanced NSCLC: French subset analysis of the ASSESS study', Journal of Thoracic Disease, vol. 11, no. 4, pp. 1370-1378. https://doi.org/10.21037/jtd.2019.03.95
Denis, Marc G. ; Lafourcade, Marie Pierre ; Le Garff, Gwenaëlle ; Dayen, Charles ; Falchero, Lionel ; Thomas, Pascal ; Locher, Chrystèle ; Oliviero, Gérard ; Licour, Muriel ; Reck, Martin ; Normanno, Nicola ; Molinier, Olivier. / Circulating free tumor-derived DNA to detect EGFR mutations in patients with advanced NSCLC : French subset analysis of the ASSESS study. In: Journal of Thoracic Disease. 2019 ; Vol. 11, No. 4. pp. 1370-1378.
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AU - Dayen, Charles

AU - Falchero, Lionel

AU - Thomas, Pascal

AU - Locher, Chrystèle

AU - Oliviero, Gérard

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AU - Normanno, Nicola

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N2 - Background: The non-interventional ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for epidermal growth factor receptor (EGFR) mutation testing in patients with advanced non-small-cell lung cancer (NSCLC), in a real-world setting across 56 centers in Europe and Japan. The high mutation status concordance between 1162 matched tissue/cytology and plasma samples (89%, sensitivity =46%, specificity =97%) suggested that ctDNA is a feasible sample for EGFR mutation analysis. We report data for the French subset of patients (pre-planned analysis). Methods: Eligible patients (stage IIIA/B/IV locally advanced/metastatic treatment-naive advanced NSCLC) provided diagnostic tissue/cytology and plasma samples. DNA extracted from tissue/cytology samples was subjected to EGFR mutation testing as per local practice; a designated laboratory performed ctDNA extraction/mutation testing of plasma samples. The primary outcome was EGFR mutation status concordance between matched tumor and plasma samples. Results: Of the 1,311 patients enrolled in the ASSESS trial, 145 were recruited from 9 centers in France. Tumor samples from 130 patients were collected and 126 were evaluable for EGFR mutation analysis. Activating EGFR mutations were identified in 13 of the 126 patient tumor samples (EGFR mutation frequency 10.3%). For plasma testing, 10 of the 145 samples tested were positive for EGFR mutations (EGFR mutation frequency 6.9%). EGFR mutation rate was significantly higher in never- versus ever-smokers (stepwise logistic regression: tumor, P<0.0001; plasma, P=0.0008). Mutation status concordance between 126 matched patient samples was 96.0% [121/126; 95% confidence intervals (CI), 91.0–98.7]. Of the 113 EGFR mutation-negative patient tissue samples, one tested plasma-positive; reanalysis of plasma via two different techniques confirmed the presence of a L858R mutation, indicating a tissue false-negative result. Based on these data, sensitivity of plasma testing was 64.3% (9/14; 95% CI, 35.1–87.2%) and its specificity was 100.0% (112/112; 95% CI, 96.8–100.0%).

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