Loehr, Andrea, Patnaik, Akash, Campbell, David, Shapiro, Jeremy, Bryce, Alan H. ORCID: 0000-0002-0206-3895, McDermott, Ray, Sautois, Brieuc, Vogelzang, Nicholas J., Bambury, Richard M., Voog, Eric, Zhang, Jingsong, Piulats, Josep M., Hussain, Arif, Ryan, Charles J., Merseburger, Axel S., Daugaard, Gedske, Heidenreich, Axel, Fizazi, Karim, Higano, Celestia S., Krieger, Laurence E., Sternberg, Cora N., Watkins, Simon P., Despain, Darrin, Simmons, Andrew D., Dowson, Melanie, Golsorkhi, Tony, Chowdhury, Simon and Abida, Wassim (2021). Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study. Clin. Cancer Res., 27 (24). S. 6677 - 6687. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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Abstract

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA(+)), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report dinical efficacy in patients with BRCA(+) mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA(+) identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA(+) by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA(+) mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Loehr, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patnaik, AkashUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campbell, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shapiro, JeremyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bryce, Alan H.UNSPECIFIEDorcid.org/0000-0002-0206-3895UNSPECIFIED
McDermott, RayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sautois, BrieucUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogelzang, Nicholas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bambury, Richard M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voog, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, JingsongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piulats, Josep M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hussain, ArifUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ryan, Charles J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merseburger, Axel S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daugaard, GedskeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heidenreich, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fizazi, KarimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Higano, Celestia S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krieger, Laurence E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sternberg, Cora N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Watkins, Simon P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Despain, DarrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simmons, Andrew D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dowson, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Golsorkhi, TonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chowdhury, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abida, WassimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-606763
DOI: 10.1158/1078-0432.CCR-21-2199
Journal or Publication Title: Clin. Cancer Res.
Volume: 27
Number: 24
Page Range: S. 6677 - 6687
Date: 2021
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1557-3265
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CIRCULATING TUMOR DNA; TISSUE ACQUISITION; BONE-BIOPSY; MUTATION; PROFILEMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60676

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