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
| Autor: | Darrin Despain, Andrea Loehr, Akash Patnaik, Daniel P. Petrylak, Thomas S. Stanton, Wassim Abida, Robert J. Amato, Simon Chowdhury, Charles J. Ryan, Andrew Simmons, Howard I. Scher, Ivor John Percent, Raymond S. McDermott, Arif Hussain, Alan H. Bryce, Anthony A. Golsorkhi, Jingsong Zhang, Simon Paul Watkins, Nicholas J. Vogelzang, Jeremy Shapiro |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty business.industry Somatic cell medicine.disease Germline 03 medical and health sciences Prostate cancer chemistry.chemical_compound Prostate-specific antigen 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Internal medicine PARP inhibitor medicine Orchiectomy business Rucaparib Allele frequency 030215 immunology |
| Zdroj: | Journal of Clinical Oncology. 37:5031-5031 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2019.37.15_suppl.5031 |
| Popis: | 5031 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. [Table: see text] |
| Databáze: | OpenAIRE |
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