In the PROPHECY study, reported in the Journal of Clinical Oncology, Armstrong et al found that positive findings on 2 assays for circulating tumor cell (CTC) androgen receptor splice variant 7 (AR-V7) were associated with poorer outcomes for abiraterone and enzalutamide therapy in men with high-risk metastatic castration-resistant prostate cancer.
In the multicenter, prospective, blinded study, the primary objective was to validate the prognostic significance of baseline CTC AR-V7 for radiographic or clinical progression free-survival using the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear-specific AR-V7 protein assay. The study included 118 men with high-risk metastatic castration-resistant prostate cancer starting abiraterone acetate or enzalutamide treatment. Among the patients, 55 were treated with abiraterone, 58 with enzalutamide, and 5 with both concurrently.
AR-V7 Status and Outcomes
No differences in outcomes between therapies was observed, with results thus being combined in the analysis. At baseline, 28 patients (24%) were AR-V7–positive, 88 (75%) were AR-V7–negative, and 2 (1%) were unevaluable on the Johns Hopkins assay; 11 (9%) were AR-V7–positive, 96 (82%) AR-V7–negative, and 11 (9%) were unevaluable on the Epic assay. The percentage agreement between the 2 assays was 82%.
AR-V7 detection by both the Johns Hopkins and Epic AR-V7 assays was independently associated with poorer progression-free survival and overall survival after adjustment for CTC number and clinical prognostic factors. For the Johns Hopkins assay, AR-V7 detection was associated with hazard ratios of 1.9 (P = .032) for progression-free survival and 4.2 (95% confidence interval [CI] = 2.1–8.5) for overall survival. For the Epic AR-V7 assay, AR-V7 detection was associated with hazard ratios of 2.4 (P = .020) for progression-free survival and 3.5 (95% CI = 1.6–8.1) for overall survival.
Patients with AR-V7–positive disease on the assays had fewer confirmed prostate-specific antigen responses (0% to 11%) and soft-tissue responses (0% to 6%) vs AR-V7–negative patients. At progression on abiraterone or enzalutamide, 14 (20%) of 69 evaluable patients had AR-V7 detection on Epic assay criteria and 26 (34%) of 77 evaluable patients had AR-V7 detection on Johns Hopkins assay criteria, suggesting induction or selection of AR-V7 expression.
The investigators concluded, “Detection of AR-V7 in CTCs by two blood-based assays is independently associated with shorter [progression-free and overall survival] with abiraterone or enzalutamide, and such men with metastatic castration-resistant prostate cancer should be offered alternative treatments.”
Andrew J. Armstrong, MD, of Duke University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a grant from the Prostate Cancer Foundation, Movember, and Department of Defense Prostate Cancer Clinical Trials Consortium. The study authors' full disclosures can be found at jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.