Genomic characteristics of deleterious BRCA1 and BRCA2 alterations and associations with baseline clinical factors in patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in TRITON2.

Authors

null

Wassim Abida

Memorial Sloan Kettering Cancer Center, New York, NY

Wassim Abida , Alan Haruo Bryce , Nicholas J. Vogelzang , Robert J. Amato , Ivor John Percent , Jeremy David Shapiro , Raymond S. McDermott , Arif Hussain , Akash Patnaik , Daniel Peter Petrylak , Charles J. Ryan , Thomas S. Stanton , Jingsong Zhang , Andrea Loehr , Andrew Simmons , Darrin Despain , Anthony A. Golsorkhi , Simon Paul Watkins , Howard I. Scher , Simon Chowdhury

Organizations

Memorial Sloan Kettering Cancer Center, New York, NY, Mayo Clinic, Phoenix, AZ, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, The University of Texas Health Science Center, Houston, TX, Florida Cancer Specialists, Port Charlotte, FL, Cabrini Hospital, Malvern, VIC, Australia, Adelaide and Meath Hospital (Incorporating the National Children's Hospital), Dublin, Ireland, University of Maryland Greenebaum Cancer Center, Baltimore, MD, University of Chicago Comprehensive Cancer Center, Chicago, IL, Yale University, Yale Cancer Center, New Haven, CT, University of Minnesota, Minneapolis, MN, St. Joseph Health Cancer Center, Santa Rosa, CA, H. Lee Moffitt Cancer Center, Tampa, FL, Clovis Oncology, Inc., Boulder, CO, Guy's Hospital and Sarah Cannon Research Institute, London, United Kingdom

Research Funding

Pharmaceutical/Biotech Company

Background: The phase 2 TRITON2 study (NCT02952534) is evaluating the PARP inhibitor rucaparib in patients with mCRPC who have a deleterious germline or somatic alteration in BRCA (BRCA1 or BRCA2) or 1 of 13 other DNA damage repair genes. Here we present analyses of tumor genomics and baseline clinical characteristics in mCRPC patients with a deleterious alteration in BRCA. Methods: Plasma (baseline) and tissue (archival or baseline) samples from patients with a deleterious alteration in BRCA were analyzed using Foundation Medicine next-generation sequencing assays. The alterations and zygosity of the alterations that were detected, as well as the somatic/germline status from Color Genomics testing, were summarized. Associations between genomic alterations, DNA yield, allele frequency, and baseline clinical characteristics were investigated. Results: Results are shown in the Table for a cohort of 40 BRCA2 and 5 BRCA1 patients enrolled in TRITON2 (Abida W et al. Presented at ESMO 2018. Abst 793PD). A biallelic alteration was observed in 21 of the 22 BRCA2 patients (95%) for whom alteration zygosity could be determined. Among the 5 BRCA1 patients, 1 alteration was monoallelic and 4 were of unknown zygosity. Co-occurring alterations in cancer-related or DNA damage repair genes were observed in many patients with BRCA alterations. At baseline, cell-free DNA (cfDNA) yield correlated positively with the sum of target lesions (STL; P= 0.04), but not with prostate-specific antigen (PSA) levels (P= 0.86). No correlation was observed between allele frequency of the BRCA alteration baseline STL (P= 0.68) or PSA levels (P= 0.97). Conclusions: Patients with a BRCA mutation enrolled in TRITON2 demonstrate a profile of genomic alterations consistent with that of prior studies of patients with mCRPC. Plasma cfDNA profiling showed a correlation between baseline cfDNA yield and measurable tumor burden, but not baseline PSA. Clinical trial information: NCT02952534

n (%)BRCA1 (n = 5)BRCA2 (n = 40)
Alteration type
Frameshift alteration2 (40%)20 (50%)
Homozygous loss0 (0%)12 (30%)
Germline/somatic status
Germline2 (40%)13 (33%)
Somatic3 (60%)27 (67%)

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary (Prostate) Cancer

Track

Genitourinary Cancer—Prostate, Testicular, and Penile

Sub Track

Prostate Cancer - Advanced Disease

Clinical Trial Registration Number

NCT02952534

Citation

J Clin Oncol 37, 2019 (suppl; abstr 5031)

DOI

10.1200/JCO.2019.37.15_suppl.5031

Abstract #

5031

Poster Bd #

143

Abstract Disclosures