Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 19:10.1158/1078-0432.CCR-24-3531.
doi: 10.1158/1078-0432.CCR-24-3531. Online ahead of print.

Concordance between tumor tissue and plasma DNA genotyping in the NCI-MATCH trial (EAY131)

Mohamed A Gouda  1 , Filip Janku  1 , Ying Yuan  2 , Leylah M Drusbosky  3 , Alice P Chen  4 , Xiaofeng Zheng  1 , Keyur Patel  2 , Stanley R Hamilton  5 , Mark Routbort  2 , James V Tricoli  6 , P Mickey Williams  7 , A John Iafrate  8 , Jeffrey Sklar  9 , Brent Coffey  6 , Richard F Little  4 , Carlos L Arteaga  10 , Peter J O'Dwyer  11 , Keith T Flaherty  12 , Lyndsay N Harris  6 , Funda Meric-Bernstam  2
Affiliations

Concordance between tumor tissue and plasma DNA genotyping in the NCI-MATCH trial (EAY131)

Mohamed A Gouda et al. Clin Cancer Res. .

Abstract

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

Patients and methods: 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.

Results: 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 non-contemporaneous tissue and plasma samples. Variations in concordance rates were observed with different alteration types, by maximum plasma variant allelic frequency, and based on tumor biopsy site.

Conclusions: 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 patients' enrollment in trials evaluating biomarker-driven anticancer therapies.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: MAG reported advisory board for Caris Life Sciences. FJ holds a leadership position in Monte Rosa Therapeutics and has ownership interest in Monte Rosa Therapeutics. YY served as a statistical consultant to AbbVie, Affinixttx, Amgen, Ascendis, Bexion, Boehringer Ingelheim, Boren Hospital, Bristol Myers Squibb, Century, Frontier Medicine, GT Medical, NeoImmueTech, Merck, NextCure, Repare, Servier, Starpax, Transthera, Xinthera, and Vertex. FMB reports consulting for AbbVie, Aduro BioTech Inc., Alkermes, AstraZeneca, Daiichi Sankyo Co. Ltd., Calibr (a division of Scripps Research), DebioPharm, Ecor1 Capital, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., GT Apeiron, Genentech Inc., Harbinger Health, IBM Watson, Incyte, Infinity Pharmaceuticals, Jackson Laboratory, Kolon Life Science, LegoChem Bio, Lengo Therapeutics, Menarini Group, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Protai Bio Ltd, Samsung Bioepis, Seattle Genetics Inc., Tallac Therapeutics, Tyra Biosciences, Xencor, Zymeworks; advisory committee membership for Black Diamond, Biovica, Eisai, FogPharma, Immunomedics, Inflection Biosciences, Karyopharm Therapeutics, Loxo Oncology, Mersana Therapeutics, OnCusp Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Sanofi, Silverback Therapeutics, Spectrum Pharmaceuticals, Theratechnologies, Zentalis; sponsored research (to the institution) from Aileron Therapeutics, Inc. AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Klus Pharma, Takeda Pharmaceutical, Novartis, Puma Biotechnology Inc., Taiho Pharmaceutical Co.; honoraria from Dava Oncology; and Other (Travel Related) from European Organization for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO), Cholangiocarcinoma Foundation, Dava Oncology. The remaining authors declare no potential conflicts of interest.

Similar articles

See all similar articles

References

    1. Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic - implementation issues and future challenges. Nat Rev Clin Oncol 2021;18(5):297–312 10.1038/s41571-020-00457-x. - DOI - PubMed
    1. Krebs MG, Malapelle U, Andre F, Paz-Ares L, Schuler M, Thomas DM, et al. Practical Considerations for the Use of Circulating Tumor DNA in the Treatment of Patients With Cancer: A Narrative Review. JAMA Oncol 2022. 10.1001/jamaoncol.2022.4457. - DOI - PubMed
    1. Gouda MA, Huang HJ, Piha-Paul SA, Call SG, Karp DD, Fu S, et al. Longitudinal Monitoring of Circulating Tumor DNA to Predict Treatment Outcomes in Advanced Cancers. JCO Precis Oncol 2022;6:e2100512 10.1200/PO.21.00512. - DOI - PMC - PubMed
    1. Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet 2019;20(2):71–88 10.1038/s41576-018-0071-5. - DOI - PubMed
    1. Mack P, Minichielle K, Redman M, Tolba K, Kozono D, Waqar S, et al. LUNGMAP Master Protocol (LUNGMAP): Concordance Between Plasma ctDNA and Tissue Molecular Analysis. Journal of Thoracic Oncology 2021;16(3):S163–S4 10.1016/j.jtho.2021.01.196. - DOI

LinkOut - more resources