The positive detection of androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) was independently associated with worse survival outcomes among men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide according to results of the PROPHECY study, which were reported in the Journal of Clinical Oncology.1 

The PROPHECY study (ClinicalTrials.gov Identifier: NCT02269982) assessed the prognostic significance of two AR-V7 assays, and the study findings suggest that either assay could help identify men who are unlikely to benefit from treatment with abiraterone or enzalutamide and should be offered alternative therapies instead.

The prospective, multicenter, blinded PROPHECY study included 118 men across 5 cites with high-risk mCRPC who were beginning treatment with either abiraterone or enzalutamide. Men who had received abiraterone or enzalutamide previously were eligible as long as they received the alternative therapy in the trial. A total of 55 men received abiraterone, 58 received enzalutamide, and 5 received both at the same time. 

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Blood samples were collected at baseline before treatment, and the presence of AR-V7 in CTCs was assessed using two AR-V7 assays: the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear-specific AR-V7 protein assay, which is commercially available. 

Overall, 24% of men had AR-V7 positivity at baseline according to the Hopkin’s AR-V7 assay and 9% of men had AR-V7 positivity at baseline according to the Epic AR-V7 assay. Between the 2 assays, an 82% concordance was seen, with the greatest discordance seen among 17 patients who tested AR-V7 positive via the Hopkins AR-V7 assay but negative via the Epic AR-V7 assay.

“Eighty-two percent is high concordance,” Tanya Dorff, MD, medical oncologist at City of Hope, California, told Cancer Therapy Advisor. She was not involved in the PROPHECY study. “On the other hand, one limitation is that these [assays] were CTC-based, and so a patient without CTCs was called AR-V7 negative. We might have missed people who had AR-V7 just because we didn’t get a CTC.”