Association of AR-V7 and Prostate-Specific Antigen RNA Levels in Blood with Efficacy of Abiraterone Acetate and Enzalutamide Treatment in Men with Prostate Cancer

• Published in: Clinical cancer research 2017-02, Vol.23 (3), p.726-734
• Main Authors: Qu, Fangfang, Xie, Wanling, Nakabayashi, Mari, Zhang, Haitao, Jeong, Seong Ho, Wang, Xiaodong, Komura, Kazumasa, Sweeney, Christopher J, Sartor, Oliver, Lee, Gwo-Shu Mary, Kantoff, Philip W
• Format: Article
• Language: English
• Subjects: Abiraterone Acetate - therapeutic use; Acetic acid; Adenocarcinoma - blood; Adenocarcinoma - drug therapy; Aged; Aged, 80 and over; Alternative splicing; Androgen Antagonists - therapeutic use; Androgen receptors; Androgens; Antineoplastic Agents, Hormonal - therapeutic use; Biomarkers; Biomarkers, Tumor - blood; Blood; Cancer; Castration; Confidence intervals; Experimental design; Gene expression; Humans; Kallikreins - blood; Kallikreins - genetics; Kaplan-Meier Estimate; Male; Medical prognosis; Middle Aged; Neoplasms, Hormone-Dependent - blood; Neoplasms, Hormone-Dependent - drug therapy; Patients; Peripheral blood; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - therapeutic use; Prognosis; Proportional Hazards Models; Prostate cancer; Prostate-specific antigen; Prostate-Specific Antigen - blood; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Protein Isoforms - genetics; Receptors, Androgen - genetics; Regression analysis; Retrospective Studies; Ribonucleic acid; RNA; RNA, Messenger - blood; RNA, Neoplasm - blood; Statistical analysis; Steroid 17-alpha-Hydroxylase - antagonists & inhibitors; Transcription; Tumor cells
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-16-1070

We evaluated the association of PSA and androgen receptor splice variant-7 (AR-V7) transcript levels in patients' blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate and/or enzalutamide treatment in castration-resistant prostate cancer (CRPC) patients. RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using droplet digital-PCR in retrospective cohorts treated with abiraterone acetate (N = 81) or enzalutamide (N = 51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses. PSA transcripts were detected in 57% of abiraterone acetate-treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95% confidence interval (CI) 1.26-4.10) and 2.60 (95% CI, 1.19-5.69); P = 0.006 and 0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P = 0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in enzalutamide cohort). In multivariable models, the association with TTF remained significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01-4.05; P = 0.048), but statistically insignificant in the abiraterone acetate cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS. PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells. Clin Cancer Res; 23(3); 726-34. ©2016 AACR.