Aberrations in androgen receptor ctDNA varies by race in metastatic castrate-resistant prostate cancer.

Abstract

247 Background: Characterization of circulating free DNA (ctDNA) may aid understanding of the pathophysiology of metastatic castrate resistant prostate cancer (mCRPC). The goal of this study was to evaluate and compare somatic alterations in ctDNA between African-American (AA) and Caucasian (C) mCRPC patients. Methods: 24 AA were retrospectively case-matched by prior treatment with 45 CA mCRPC; ctDNA was assessed with Guardant360 assay (Guardant Health, Redwood City, CA). Mutant allelic fraction, mutations, and gene amplification were compared. Results: Prior to testing, 6 AA pts and 12 CA pts had 0 lines of CRPC therapy, 7 AA pts and 10 CA pts had 1-2 lines, 5 AA and 17 CA had 3-4 lines, 5 AA and 2 CA had 5-6 lines, and 1 AA pt and 4 CA pts had >6 lines. The median Gleason score was 8, regardless of race. The median ctDNA mutant allelic fraction was 0.40% for AA pts and 0.60% for the CA pts. Mutations and/or amplifications in individually assessed genes are shown in the Table. No statistically significant differences were detected except for the androgen receptor (AR) gene where alterations (mutations and/or amplifications) were more frequent in AA as compared to C (p=0.04). Conclusions: AR alterations were more commonly detected in ctDNA in AA men as compared to C suggesting that AR driven pathophysiology may predominate in this setting. Additional analyses with a larger cohorts are warranted. Data from prospective trials in mCRPC using abiraterone/prednisone (George et al. LBA 5009, ASCO 2018) similarly suggest that mCRPC may be comparatively more AR driven in this racial setting. Alterations in ctDNA compared between AA and C men with mCRPC. [Table: see text]