Sistema de Salut de Catalunya
Institut Català de la Salut
[Chi KN] BC Cancer Agency, Vancouver, Canada. [Barnicle A] Translational Medicine, AstraZeneca, Cambridge, United Kingdom. [Sibilla C, Corcoran C] Precision Medicine and Biosamples, AstraZeneca, Cambridge, United Kingdom. [Lai Z, Barrett JC] Translational Medicine, AstraZeneca, Waltham, Massachusetts. [Mateo J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-05-11T07:14:03Z
2023-05-11T07:14:03Z
2023-01-04
Circulating tumor DNA; Prostate cancer
ADN tumoral circulante; Cáncer de próstata
ADN tumoral circulant; Càncer de pròstata
Purpose: Not all patients with metastatic castration-resistant prostate cancer (mCRPC) have sufficient tumor tissue available for multigene molecular testing. Furthermore, samples may fail because of difficulties within the testing procedure. Optimization of screening techniques may reduce failure rates; however, a need remains for additional testing methods to detect cancers with alterations in homologous recombination repair genes. We evaluated the utility of plasma-derived circulating tumor DNA (ctDNA) in identifying deleterious BRCA1, BRCA2 (BRCA), and ATM alterations in screened patients with mCRPC from the phase III PROfound study. Patients and Methods: Tumor tissue samples were sequenced prospectively at Foundation Medicine, Inc. (FMI) using an investigational next-generation sequencing (NGS) assay based on FoundationOne®CDx to inform trial eligibility. Matched ctDNA samples were retrospectively sequenced at FMI, using an investigational assay based on FoundationOne®Liquid CDx. Results: 81% (503/619) of ctDNA samples yielded an NGS result, of which 491 had a tumor tissue result. BRCA and ATM status in tissue compared with ctDNA showed 81% positive percentage agreement and 92% negative percentage agreement, using tissue as reference. At variant-subtype level, using tissue as reference, concordance was high for nonsense (93%), splice (87%), and frameshift (86%) alterations but lower for large rearrangements (63%) and homozygous deletions (27%), with low ctDNA fraction being a limiting factor. Conclusions: We demonstrate that ctDNA can greatly complement tissue testing in identifying patients with mCRPC and BRCA or ATM alterations who are potentially suitable for receiving targeted PARP inhibitor treatments, particularly patients with no or insufficient tissue for genomic analyses.
This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp.
Article
Published version
English
Cèl·lules canceroses; Medicaments antineoplàstics; Pròstata - Càncer; DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant; CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::Cell-Free Nucleic Acids::Circulating Tumor DNA; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración; COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ácidos nucleicos libres de células::ADN tumoral circulante; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
American Association for Cancer Research
Clinical Cancer Research;29(1)
https://doi.org/10.1158/1078-0432.CCR-22-0931
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
Articles científics - HVH [3439]
