Liquid Biopsy Combo Improved Sensitivity for EGFR Mutations in NSCLC

January 3, 2018

The combination of exosomal RNA and cell-free DNA improved the sensitivity of blood-based liquid biopsy for EGFR mutation detection in non–small-cell lung cancer compared with standard circulating tumor DNA.

The combination of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) improved the sensitivity of blood-based liquid biopsy for EGFR mutation detection in non–small-cell lung cancer (NSCLC) compared with standard circulating tumor DNA (ctDNA), according to a new study.

“The proportion of patients with detectable ctDNA varies by indication, stage of disease, tumor burden, and other clinical characteristics,” wrote study authors led by Johan Skog, PhD, of Exosome Diagnostics, in Waltham Massachusetts (the company provided the plasma exoRNA isolation technology used in this study). “One means to overcome the challenge of mutation detection in patients with limited ctDNA could be to include the tumor-associated RNA derived from exosomes.”

The new study included pretreatment tumor and plasma samples from 84 patients enrolled in the TIGER-X trial, which was a phase I/II study of rociletinib in NSCLC patients with mutant EGFR. A combination of exoRNA and cfDNA (exoNA) was analyzed for mutations, and compared to existing data from the same samples using ctDNA. The results were published in Annals of Oncology.

Among 54 samples that had valid tumor tissue, the sensitivity of the exoNA for finding activating EGFR mutations was 98% (53 of 54). This was significantly better than ctDNA, which had a sensitivity of 82% (44 of 54; P = .004). The results were similar for T790M mutations, for which exoNA had a sensitivity of 90% (44 of 49 available samples), and ctDNA had a sensitivity of 84% (41 of 49).

In a subgroup of 50 patients who had low-copy T790M (< 10 copies/mL), the sensitivity was 81% with exoNA and 58% with ctDNA for activating EGFR mutations (P = .003). For T790M mutations, exoNA had a sensitivity of 61% while ctDNA had a sensitivity of 53% (P = .5).

The difference was greatest in another subgroup of 21 patients with intrathoracic (M0/M1a) disease. In those patients, the sensitivity for activating mutations was 74% with exoNA and 26% with ctDNA (P = .003); for T790M mutations the rates were 31% and 19%, respectively (P = .5).

“The increase in sensitivity when using exoNA was not accompanied by a significant difference in specificity,” the authors wrote. The exoNA test “could be especially beneficial in cases with low levels of nucleic acids in circulation, such as patients with low tumor burden, intrathoracic disease, or for early detection of cancer.”