759PD - Ar and Cyp17A1 Copy Number Variations May Predict Clinical Outcome of Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone

Abstract

ABSTRACT Aim: Abiraterone acetate is a potent inhibitor of cytochrome P450 17 alpha-hydrolase (CYP17A1) causing decrease of synthesis of testosterone in the adrenal glands, testicles and tumor microenvironment with survival advantage in patients with metastatic castration-resistant prostate cancer (CRPC). We analyzed the predictive role of copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes, in serum cell free DNA of CRPC patients treated with abiraterone. Patients and methods: The study was conducted on a consecutive series of 53 CRPC patients treated with abiraterone after at least one chemotherapeutic regimen with docetaxel. DNA was isolated from serum collected before starting abiraterone treatment and CNVs were analyzed for AR and CYP17A1 genes using Taqman copy number assays. Results: AR gene resulted amplified in 16 cases, CYP17A1 in 15. 10 cases were amplified for both genes. The median progression-free survival (PFS) of patients with AR gene amplification was 2.8 vs. 9.5 months of normal individuals. Patients with CYP17A1 gene amplification had a median PFS of 2.8 months vs. 9.2 months in the diploid patients. A lower overall survival (OS) was reported in patients with AR and CYP17A1 gene amplification (AR: P Conclusions: The CNVs of AR and CYP17A1 genes are promising markers predicting outcome in patients with CRPC treated with abiraterone. Further studies are warranted to validate these biomarkers to be used through a “liquid biopsy”, for outcome prediction to abiraterone in these patients. Disclosure: All authors have declared no conflicts of interest.