Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma

Abstract

Background

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. We 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.

Patients and methods

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.

Results

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.

Conclusions

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.

Clinical Trials

NCT01526928