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J Thorac Dis. 2019 Apr;11(4):1370-1378. doi: 10.21037/jtd.2019.03.95.

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

Author information

1
Department of Biochemistry and INSERM U1232, Nantes University Hospital, 9 quai Moncousu, F-44093 Nantes Cedex, France.
2
Centre Hospitalier D'Angoulême, rond-point Girac, 16470 Saint Michel, France.
3
Centre Hospitalier Hôpital Yves Le Foll, 10 r Marcel Proust, 22027 St Brieuc, France.
4
Centre Hospitalier De Saint Quentin, 1 av Michel de l'Hôpital, Saint-Quentin, France.
5
Centre Hospitalier Villefranche-Sur-Saône, 69655 Villefranche-sur-Saône Cedex, France.
6
Centre Hospitalier Intercommunal des Alpes du Sud, 1 pl Auguste Muret, 05007 Gap, France.
7
Centre Hospitalier de Meaux, 6-8 r Saint Fiacre, 77104 Meaux, France.
8
Centre Hospitalier de Longjumeau, 159 r Prés François Mitterrand, 91160 Longjumeau, France.
9
AstraZeneca, Tour Carpe Diem, 31 place des Corolles, 92400 Courbevoie, France.
10
Department of Thoracic Oncology, LungenClinic Grosshansdorf GmbH, Airway Research Centre North, Member of the German Centre for Lung Research (DZL), Grosshansdorf, Germany.
11
Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione Pascale", IRCCS, Naples, Italy.
12
Centre Hospitalier Du Mans, 194 av Rubillard, 72037 Le Mans, France.

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%).

Conclusions:

Data confirm ctDNA as an alternative sample for EGFR mutation analysis in patients with advanced NSCLC.

KEYWORDS:

Non-small cell lung cancer (NSCLC); circulating tumor DNA; epidermal growth factor receptor (EGFR); plasma

Conflict of interest statement

Conflicts of Interest: MG Denis: grants/research support/consultant for AstraZeneca, BMS, Boehringer Ingelheim, Merck, Qiagen, Roche Pharma, and Takeda. G Le Garff: clinical trials for AstraZeneca, Lilly, and Roche; all financial contributions except MUTACT study (AstraZeneca) paid by clinical research unit; board member for Novartis; invitation to congress from Air Santé, Altana, AstraZeneca (before 2012), Boehringer Ingelheim, GSK, LFB, Lilly, MSD, Pierre Fabre, and Roche. C Locher: membership on advisory board for AstraZeneca, BMS, Boehringer Ingelheim, Pfizer, and Roche; medical conferences for Novartis. M Licour: employee of AstraZeneca. N Normanno: grants/research support/consultant for AstraZeneca, Qiagen, and Roche Diagnostics. M Reck: member of the speaker’s bureau for AstraZeneca, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Hoffmann-La Roche, Lilly, and Pfizer; consultant for AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Lilly, MSD, and Pfizer. All other authors have declared no conflicts of interest.

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