Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study
AuthorsRothwell, Dominic G
Thistlethwaite, Fiona C
Dean, Emma J
Smith, Nigel K
White, Daniel J
Frese, Kristopher K
Miller, Crispin J
Jordan, Allan M
O'Brien, Ciara S
Vickers, Alexander J
Hughes, Andrew M
Krebs, Matthew G
AffiliationClinical Experimental Pharmacology Group, CRUK Manchester Institute, Manchester, UKClinical Experimental Pharmacology Group, CRUK Manchester Institute, Manchester, UK
MetadataShow full item record
AbstractNext-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. When a 2.5% variant allele frequency (VAF) threshold was applied, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. These data support the application of ctDNA in this early phase trial setting where broad genomic profiling of contemporaneous tumor material enhances patient stratification to novel therapies and provides a practical template for bringing routinely applied blood-based analyses to the clinic.
CitationRothwell DG, Ayub M, Cook N, Thistlethwaite F, Carter L, Dean E, et al. Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study. Nat Med. 2019; 25(5):738-43.
- Clinical utility of plasma-based digital next-generation sequencing in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping.
- Authors: Zugazagoitia J, Ramos I, Trigo JM, Palka M, Gómez-Rueda A, Jantus-Lewintre E, Camps C, Isla D, Iranzo P, Ponce-Aix S, García-Campelo R, Provencio M, Franco F, Bernabé R, Juan-Vidal O, Felip E, de Castro J, Sanchez-Torres JM, Faul I, Lanman RB, Garrido P, Paz-Ares L
- Issue date: 2019 Feb 1
- Correlation of genomic alterations between tumor tissue and circulating tumor DNA by next-generation sequencing.
- Authors: Chang YS, Fang HY, Hung YC, Ke TW, Chang CM, Liu TY, Chen YC, Chao DS, Huang HY, Chang JG
- Issue date: 2018 Nov
- Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer.
- Authors: Tarazona N, Gimeno-Valiente F, Gambardella V, Zuñiga S, Rentero-Garrido P, Huerta M, Roselló S, Martinez-Ciarpaglini C, Carbonell-Asins JA, Carrasco F, Ferrer-Martínez A, Bruixola G, Fleitas T, Martín J, Tébar-Martínez R, Moro D, Castillo J, Espí A, Roda D, Cervantes A
- Issue date: 2019 Nov 1
- Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Circulating Tumor DNA in Breast Cancer.
- Authors: Chae YK, Davis AA, Jain S, Santa-Maria C, Flaum L, Beaubier N, Platanias LC, Gradishar W, Giles FJ, Cristofanilli M
- Issue date: 2017 Jul
- Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer.
- Authors: Wyatt AW, Annala M, Aggarwal R, Beja K, Feng F, Youngren J, Foye A, Lloyd P, Nykter M, Beer TM, Alumkal JJ, Thomas GV, Reiter RE, Rettig MB, Evans CP, Gao AC, Chi KN, Small EJ, Gleave ME
- Issue date: 2017 Dec 1