Abstract B007: Concordance between tumor tissue and plasma genotyping in NCI-MATCH Trial (EAY131)
Authors: Gouda Mohamed A , Janku Filip , Yuan Ying , Drusbosky Leylah , Chen Alice P , Patel Keyur , Hamilton Stanley R , Routbort Mark , Williams P. Mickey , Iafrate John , Sklar Jeffrey , Coffey Brent , Little Richard F , Arteaga Carlos L , Abrams Jeffrey S , O’Dwyer Peter J , Flaherty Keith T , Harris Lyndsay N , Meric-Bernstam Funda 
Published: December 2023

Background: Utilization of liquid biopsy has become increasingly prevalent in the field of cancer therapeutics over the past decade. However, there remain unanswered questions that need to be addressed including better understanding of concordance between tumor tissue and plasma-derived circulating tumor DNA (ctDNA) from the same patient. In this study, we present the results of plasma ctDNA analysis by next-generation sequencing (NGS) in patients participating in selected arms of the NCI-MATCH Trial, with a focus on concordance between tumor tissue and plasma findings.

Methods: Our study included patients treated on the NCI-MATCH Trial (NCT02465060) who had their plasma samples collected within 90 days before commencing treatment. 16 out of 39 treatment subprotocols of NCI-MATCH Trial were included in this plasma analysis protocol. Plasma samples were tested using the Guardant360 NGS assay (Guardant Health) and tumor tissue NGS results were obtained through central testing by the Oncomine assay (ThermoFisher). Concordance was defined as the detection of the same gene alteration leading to patient enrollment in NCI-MATCH trial, in both tissue and plasma.

Results: Our study included 334 patients with a variety of tumor types who had baseline plasma samples. Plasma sequencing data were available in 328 patients; of whom 326 (99.4%) had a total of 2,779 alterations in plasma (2,055 somatic [74%] and 724 presumed germline [26%]). The tissue alteration of interest was detected in plasma of 196 (76.9%) of 255 patients enrolled based on central lab testing who had contemporaneous plasma and tissue samples. The concordance rate was higher in patients with tissue biopsies obtained from metastatic sites compared to patients with tissue biopsies obtained from primary tumor (79.9% [n=183] vs 45.5% [n=10], p&lt;0.001). Concordance was highest for copy number variations (82.5%, n=52), single nucleotide variants (79.5%, n=124) and insertions/deletions (75%, n=12), while lower concordance rates were found for gene fusions (40%, n=8). A lower concordance rate was observed in 73 patients enrolled based on outside designated lab tissue testing (43.8% [n=32]). Notably, these patients had a median interval between plasma and tissue samples of 239 days (range; 38-1917). However, concordance was also higher in this group with samples collected from metastatic sites compared to primary tumors (62.5% vs 26.5%, p=0.003).

Conclusions: In the NCI-MATCH Trial, the tumor tissue alteration of interest was detected in plasma of 76.9% of patients who had contemporaneous tissue and plasma samples, suggesting a potential role for liquid biopsy in patients’ enrollment. Concordance rates varied according to type of alteration of interest, and site of tissue sample (primary versus metastatic tumor), as well as the interval between sampling of tissue and plasma.

Citation Format: Mohamed A Gouda, Filip Janku, Ying Yuan, Leylah Drusbosky, Alice P Chen, Keyur Patel, Stanley R Hamilton, Mark Routbort, P. Mickey Williams, John Iafrate, Jeffrey Sklar, Brent Coffey, Richard F Little, Carlos L Arteaga, Jeffrey S Abrams, Peter J O’Dwyer, Keith T Flaherty, Lyndsay N Harris, Funda Meric-Bernstam. Concordance between tumor tissue and plasma genotyping in NCI-MATCH Trial (EAY131) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B007.