Prevalence of HRR gene mutations in patients with metastatic castration-resistant prostate cancer: Germline results from the Latin-American observational study PROSPECT.

Abstract

226 Background: Metastatic castration-resistant prostate cancer (mCRPC) is a molecularly heterogeneous disease, and 20% to 30% of patients harbor alterations in homologous recombination repair (HRR) genes. However, data regarding the genetic profile of mCRPC in Latin American populations are scarce. This study determined the prevalence of HRR gene mutations in Latin American patients with mCRPC to better understand this population and guide future policies. The interim analysis herein reports results focused on germline alterations only. Methods: PROSPECT (NCT04962880) is a cross-sectional, non-interventional, multicenter study. Patients were adults (≥18 years) diagnosed with mCRPC from November 2020 to October 2021 at centers in Argentina, Brazil, Colombia, Costa Rica, Mexico, Panama, and Peru. Diagnoses were confirmed by laboratory testing (PSA and/or testosterone levels) or imaging (X-ray, CT, MRI, or PET scan). All patients provided written informed consent. Blood samples were assayed to determine the prevalence of germline mutations in HRR genes in the participating countries using the AmoyDx HANDLE HRR Next Generation Sequence 32 genes Panel (AmoyDx, Xiamen, China). Results: Overall, 388 participants with a median age of 70 years (range: 49‒89) were included in this study, including 184 Hispanic (47.4%), 101 White (26%), 40 Mestizo (10.3%), 11 African American (2.8%), 2 Asian (0.5%), and 50 “other” (12.9%) patients. Over a third of them (n=151, 38.9%) had a family history of cancer. Median time since prostate cancer diagnosis was 3 years (range: 0‒23) and 2 years (range: 0‒22) since mCRPC diagnosis. Metastases were most frequently localized to the bones (59.6%). The patients’ ECOG status was either 0 (173/365; 47.4%) or 1 (192/365; 52.6%). Among the 167 patients that received treatment, most received androgen deprivation therapy alone (43.7%) or with radiotherapy (21.6%). Overall, 25/381 patients (6.56%) had germline HRR mutations. The 5 most frequently mutated HRR genes were BRCA2 (16%), ATM (12%), CHEK2 (12%), BRIP1 (8%) and HOXB13 (8%). Conclusions: The prevalence of germline HRR mutations found in this multinational Latin American population was lower than expected compared to previously reported rates ranging from 8% to 12% from other countries. Additionally, the most frequently mutated HRR genes differed from those from major trials including PROfound (NCT02987543). Clinical trial information: NCT04962880 . [Table: see text]