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

Background: The non-interventional ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for epidermal growth factor receptor () 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 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 mutation testing as per local practice; a designated laboratory performed ctDNA extraction/mutation testing of plasma samples. The primary outcome was 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 mutation analysis. Activating mutations were identified in 13 of the 126 patient tumor samples ( mutation frequency 10.3%). For plasma testing, 10 of the 145 samples tested were positive for mutations ( mutation frequency 6.9%). 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 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 mutation analysis in patients with advanced NSCLC.