759PD - AR and CYP17A1 copy number variations may predict clinical outcome of patients with metastatic castration-resistant prostate cancer treated with ab...

Date 28 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate
Topics Prostate Cancer
Pathology/Molecular Biology
Translational Research
Presenter Vincenza Conteduca
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors V. Conteduca1, S. Salvi2, V. Casadio2, S.L. Burgio1, C. Menna1, L. Rossi1, E. Bianchi1, E. Carretta3, F. Fabbri3, D. Callistri2, W. Zoli2, U. De Giorgi1
  • 1Department Of Medical Oncology, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 2Biosciences Laboratory, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 3Unit Of Biostatistics And Clinical Trials, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT

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.

Methods

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 < 0.0001; CYP17A1: P = 0.0085). At multivariate analysis, PSA decline ≥ 50%, AR and CYP17A1 CNVs were able to predict PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), whereas performance status, PSA decline ≥ 50%, AR CNV and DNA concentration predicted OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively).

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.