Next-generation sequencing of primary prostate cancer tumors to reveal actionable opportunities for clinical management.

Daniel James Crona Univ of North Carolina At Chapel Hill, Chapel Hill, NC info_outline Daniel James Crona, Anthony Drier, Jing Daisy Zhu, Emily Fox Bell, Margaret Rose Sketch, Alexandra Boland, Amy Garrett, Lin Wang, Khalis Mitchell, Scott A. Tomlins, Elizabeth Claire Dees, Paul Alphonso Godley, Mary Dunn, Tracy L Rose, Ethan M. Basch, Matthew I. Milowsky, Young E. Whang

Authors Daniel James Crona Univ of North Carolina At Chapel Hill, Chapel Hill, NC info_outline Daniel James Crona, Anthony Drier, Jing Daisy Zhu, Emily Fox Bell, Margaret Rose Sketch, Alexandra Boland, Amy Garrett, Lin Wang, Khalis Mitchell, Scott A. Tomlins, Elizabeth Claire Dees, Paul Alphonso Godley, Mary Dunn, Tracy L Rose, Ethan M. Basch, Matthew I. Milowsky, Young E. Whang Organizations Univ of North Carolina At Chapel Hill, Chapel Hill, NC, University of North Carolina at Chapel Hill, Chapel Hill, NC, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, Lineberger Comprehensive Cancer Center, University of North Caroina, Chapel Hill, NC, Strata Oncology, Ann Arbor, MI, University of Michigan, Ann Arbor, MI, The University of North Carolina at Chapel Hill, Chapel Hill, NC, Department of Medicine, Division of Hematology/Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, University of North Carolina Hospital, Chapel Hill, NC, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: The Strata Trial (NCT03061305) is a multi-institutional precision oncology collaboration structured as an observational protocol that aims to match patients to genomically guided therapies. Methods: Selected University of North Carolina (UNC) metastatic prostate cancer (mPC) patients were enrolled on this IRB-approved study. Formalin fixed paraffin-embedded primary tumor specimens, without matched germline controls, were sent for targeted next generation sequencing (NGS) to detect actionable variants, including: mutations in 87 genes, copy number variations in 31 genes, gene fusions in 46 gene drivers, and microsatellite instability (MSI) status. mPC-related genes of specific interest included: AR , ATM , BRCA1/2 , ERG , MSH2 , MSH6 , PTEN , RB1 , and TP53 . Results: Of the 108 cases sequenced, 6 (6%) failed testing. Of the 102 mPC patients with sequence data, the median age was 69 (47-86), 60 (59%) were white, 35 (34%) were black, 1 (1%) was Asian, and 6 (6%) declined to identify race. NGS data revealed 122 variants in 27 genes: 73 patients (71%) had at least one variant. Among those 73 patients, 38 (52%) had only 1 variant, 24 (33%) had 2 variants, 8 (11%) had 3 variants, and 3 (4%) had 4 variants. TMPRSS2-ERG fusions occurred most frequently (51%), followed by TP53 variants (38%), and PTEN variants (16%). Only 8% of patients had variants in DNA damage repair genes, including ATM (3%), BRCA2 (3%) and MSH2 (2%). Two patients with MSI high tumors were treated with pembrolizumab, while 4 patients with deep BRCA2 or ATM deletions were eligible for trials of PARP inhibition. Conclusions: Our UNC experience shows that a high proportion of primary prostate cancer tumors from mPC patients have genomic variants, and two patients were treated based on these data. Limited actionability may reflect the landscape of currently FDA approved mPC treatments available clinical trials, or due to short duration of follow-up after enrollment on the Strata Trial.