Combined exosomal RNA and circulating tumor DNA analysis improves EGFR mutation detection in NSCLC patient plasma

A major limitation of circulating tumor DNA (ctDNA) for somatic mutation detection has been the low level of ctDNA found in a subset of cancer patients. Researchers from Exosome Diagnostics GmbH investigated whether using a combined isolation of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) could improve blood-based liquid biopsy for EGFR mutation detection in NSCLC patients.

Matched pretreatment tumor and plasma were collected from 84 patients enrolled in TIGER-X (NCT01526928), a Ph1/2 study of rociletinib in mutant EGFR NSCLC patients. The combined isolated exoRNA and cfDNA (exoNA) was analyzed for mutations using a targeted NGS panel (EXO1000), and compared to existing data from the same samples using analysis of ctDNA by BEAMing.

For exoNA, the sensitivity was 98% for detection of activating EGFR mutations and 90% for EGFR T790M. The corresponding sensitivities for ctDNA by BEAMing were 82% for activating mutations and 84% for T790M. In a subgroup of patients with intrathoracic metastatic disease (M0/M1a; n = 21), the sensitivity increased from 26% to 74% for activating mutations (p = 0.003) and from 19% to 31% for T790M (p = 0.5) when using exoNA for detection.

 Comparison between exoNA (EXO1000) and ctDNA-only (BEAMing) platformsexosomes

Combined exosomal RNA and cell-free DNA (exoNA) was analyzed using the EXO1000 liquid biopsy platform and compared to ctDNA analysis by BEAMing (A) EGFR mutant copies found in exoNA compared to copies in ctDNA within the complete patient cohort. The triangles represent del19, hollow circles L858R, full circle L861Q (activating mutations) and squares T790M mutations; identity line shows equal copies/mL plasma. (B) Summary of EGFR detection in plasma within all tumor EGFR positives. (C) Summary of mutant copies found in exoNA and ctDNA. p-values were derived from a paired, one-tailed t-test comparing the two groups.

Combining exoRNA and ctDNA increased the sensitivity for EGFR mutation detection in plasma, with the largest improvement seen in the subgroup of M0/M1a disease patients known to have low levels of ctDNA which poses challenges for ctDNA-only based mutation detection.

Krug AK, Enderle D, Karlovich C, Priewasser T, Bentink S, Spiel A, Brinkmann K, Emenegger J, Grimm DG, Castellanos-Rizaldos E, Goldman JW, Sequist LV, Soria JC, Camidge DR, Gadgeel SM, Wakelee HA, Raponi M, Noerholm M, Skog J. (2017) Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma. Ann Oncol [Epub ahead of print]. [abstract]

Leave a Reply

Your email address will not be published. Required fields are marked *