Detection of BRCA1, BRCA2, and ATM Alterations in Matched Tumor Tissue and Circulating Tumor DNA in Patients with Prostate Cancer Screened in PROfound.
Loading...
Embargo End Date
ICR Authors
Authors
Chi, KN
Barnicle, A
Sibilla, C
Lai, Z
Corcoran, C
Barrett, JC
Adelman, CA
Qiu, P
Easter, A
Dearden, S
Oxnard, GR
Agarwal, N
Azad, A
de Bono, J
Mateo, J
Olmos, D
Thiery-Vuillemin, A
Harrington, EA
Barnicle, A
Sibilla, C
Lai, Z
Corcoran, C
Barrett, JC
Adelman, CA
Qiu, P
Easter, A
Dearden, S
Oxnard, GR
Agarwal, N
Azad, A
de Bono, J
Mateo, J
Olmos, D
Thiery-Vuillemin, A
Harrington, EA
Document Type
Journal Article
Date
2023-01-04
Date Accepted
2022-08-15
Abstract
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.
Citation
Clinical Cancer Research, 2022, pp. OF1 - OF11
Source Title
Clinical Cancer Research
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1078-0432
eISSN
1557-3265
1557-3265
1557-3265
Collections
Research Team
PrCa Targeted Therapy