Concordance between Tumor Tissue and Plasma DNA Genotyping in the NCI-MATCH Trial (EAY131)

Liquid biopsies with circulating tumor DNA (ctDNA) analysis are increasingly being utilized as a noninvasive approach to identify actionable genomic alterations in advanced/metastatic cancers. In this study, we report the correlation between ctDNA analysis of plasma samples collected from patients enrolled in the NCI-MATCH trial and tumor tissue-based sequencing.

We analyzed plasma samples collected from patients enrolled on 16 subprotocols of NCI-MATCH who had plasma samples collected within 90 days before starting treatment. Concordance was defined as the detection of the same gene alteration leading to patient enrollment in NCI-MATCH in both tissue and plasma.

We included 300 patients who were enrolled in NCI-MATCH. Most patients (81%, n = 243) were enrolled based on central tissue testing and had contemporaneous tissue and plasma samples. The tissue alteration of interest was detected in the plasma of 81.1% (n = 197) of patients. Lower rates of detection of the tissue alteration of interest were observed in samples from 57 patients who were enrolled based on outside designated laboratory testing (56.1%, n = 32) and had noncontemporaneous tissue and plasma samples. Variations in concordance rates were observed with different alteration types, by maximum plasma variant allele frequency, and based on tumor biopsy site.

The tumor tissue alteration of interest was detected in the plasma of 81% of patients who were enrolled in the NCI-MATCH trial based on central tissue testing and had contemporaneous tissue and plasma samples. This suggests a potential role for liquid biopsy in patient enrollment in trials evaluating biomarker-driven anticancer therapies. See related commentary by Russo et al., p. 4217.