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Type: Journal article
Title: 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
Author: Qu, F.
Xie, W.
Nakabayashi, M.
Zhang, H.
Jeong, S.
Wang, X.
Komura, K.
Sweeney, C.
Sartor, O.
Lee, G.
Kantoff, P.
Citation: Clinical Cancer Research, 2017; 23(3):726-734
Publisher: American Association for Cancer Research
Issue Date: 2017
ISSN: 1078-0432
Statement of
Fangfang Qu, Wanling Xie, Mari Nakabayashi, Haitao Zhang, Seong Ho Jeong, Xiaodong Wang, Kazumasa Komura, Christopher J. Sweeney, Oliver Sartor, Gwo-Shu Mary Lee and Philip W. Kantoff
Abstract: 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.
Keywords: Humans; Adenocarcinoma; Prostatic Neoplasms; Neoplasms, Hormone-Dependent; Phenylthiohydantoin; Androgen Antagonists; Steroid 17-alpha-Hydroxylase; Kallikreins; Prostate-Specific Antigen; Protein Isoforms; Receptors, Androgen; RNA, Messenger; RNA, Neoplasm; Antineoplastic Agents, Hormonal; Androgens; Prognosis; Proportional Hazards Models; Retrospective Studies; Aged; Aged, 80 and over; Middle Aged; Male; Kaplan-Meier Estimate; Biomarkers, Tumor; Abiraterone Acetate
Rights: © 2017, American Association for Cancer Research
RMID: 0030063527
DOI: 10.1158/1078-0432.CCR-16-1070
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