Androgen Receptor and CYP17A1 Copy Number Variations as Predictors of Outcomes in Patients with Metastatic Prostate Cancer Receiving Abiraterone
Abiraterone acetate is a potent inhibitor of cytochrome P450 17 alpha-hydrolase (CYP17A1), causing a decrease in the synthesis of testosterone and a demonstrated overall survival (OS) advantage in patients with metastatic castration-resistant prostate cancer (mCRPC; Ryan CI, et al. N Engl J Med. 2013;368:138-148). At ESMO 2014, Conteduca and colleagues presented the results of their study that analyzed the predictive value of the copy number variations of CYP17A1 and of androgen receptor genes in the serum cell-free DNA of patients with mCRPC who received abiraterone acetate (Conteduca V, et al. ESMO 2014: Abstract 759PD).
This study was conducted on a consecutive series of 53 patients with mCRPC who received abiraterone acetate after failing at least 1 docetaxel-based chemotherapy regimen. DNA was isolated from the patients’ serum before they received abiraterone acetate, and copy number variations were analyzed for androgen receptor genes and CYP17A1 genes.
Androgen receptor gene and CYP17A1 gene amplification were noted in 16 patients and 15 patients, respectively, and 10 patients displayed gene amplification for both genes. The median progression-free survival (PFS) in patients with androgen receptor gene amplification was 2.8 months compared with 9.5 months in patients without androgen receptor gene amplification. The PFS in patients with CYP17A1 gene amplification was 2.8 months compared with 9.2 months without amplification of this gene. A significantly lower median OS was observed in patients with androgen receptor and CYP17A1 gene amplification than in normal patients (androgen receptor amplification vs normal, P <.001; CYP17A1 amplification vs normal, P = .0085).
In a multivariate analysis, prostate-specific antigen (PSA) decline of ?50%, and androgen receptor and CYP17A1 copy number variations were able to predict PFS (P <.0001, P = .0004, and P = .045, respectively). Moreover, performance status, PSA decline of ?50%, androgen receptor copy number variations, and DNA concentration predicted OS (P = .0021, P = .0014, P = .0026, and P = .0129, respectively).
Conteduca and colleagues concluded that copy number variations in androgen receptor and CYP17A1 genes are promising noninvasive molecular biomarkers that can predict treatment outcome in patients with CRPC who were treated with abiraterone. This is yet another step in providing personalized medicine to these patients.