A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma

Abstract

DNA derived from NSCLC tumors can be detected with high sensitivity in urine and plasma, enabling diagnostic detection and monitoring of therapeutic response from these noninvasive "liquid biopsy" samples.

Circulating DNA in EGFR-mutated lung cancer

“…Reckamp et al used NGS based assays to interrogate EGFR activating mutations and T790M resistance mutation in urine or plasma of patients enrolled in the TIGER-X trial, a phase 1/2 study of rociletinib in previously treated patients with EGFR positive advanced NSCLC (46). The sensitivity of detecting EGFR mutations in urine was 80% for L858R, 83% for exon 19 deletions and 93% for T790M with a comparable sensitivity observed in plasma.…”

Lung Cancer Management: where are we in 2017?

“…The introduction of a so-called "liquid biopsy" represented a turning point in this clinical scenario and, even though a standardized method for the detection of EGFR mutations in plasma is currently lacking, results from ancillary studies in patients treated with third-generation EGFR TKIs report a sensitivity of between 51 and 70%, depending on the assay, and a specificity of approximately 77% [37][38][39] . Taken all together, these data suggest the reliability of plasma genotyping in this patient population, especially when a positive result is found.…”

EGFR inhibition in NSCLC: New findings…. and opened questions?

“…Since the co-occurrence of different molecular alterations has been associated with inferior outcomes to subsequent third-generation TKI therapy, ctDNA analysis could represent a useful tool to guide the clinicians in the selection of the best treatment strategy for each patient. In addition to plasma, urine genotyping has also shown a high sensitivity in detecting T790M mutation status, ranging from 72% to 93%, in preliminary studies including few patients (Reckamp et al, 2016), and is currently under investigation in trials including larger cohorts of patients. Interestingly combined plasma and urine testing identified 12 additional T790M positive patients who were negative on tissue and received benefit from Rociletinib therapy, and an early decrease of urine T790M levels was described in 9 patients during such treatment (Reckamp et al, 2016).…”

“…In addition to plasma, urine genotyping has also shown a high sensitivity in detecting T790M mutation status, ranging from 72% to 93%, in preliminary studies including few patients (Reckamp et al, 2016), and is currently under investigation in trials including larger cohorts of patients. Interestingly combined plasma and urine testing identified 12 additional T790M positive patients who were negative on tissue and received benefit from Rociletinib therapy, and an early decrease of urine T790M levels was described in 9 patients during such treatment (Reckamp et al, 2016). Notably it has been recently developed a novel targeted NGS approach for the detection of both driver mutations and rearrangements in ctDNA from advanced NSCLC patients.…”