mCRPC: Full-length AR Copy Number Prognostic for Outcomes

ORLANDO, FL – Full-length androgen receptor (AR-FL) copy number derived from circulating tumor cells detected using a liquid biopsy is associated with clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide, according to a study presented at 2017 Genitourinary Cancers Symposium.¹

For this prospective biomarker study, investigators enrolled 202 patients with mCRPC who were beginning therapy with abiraterone or enzalutamide and consented to collection of circulating tumor cells. Median follow-up was 12.9 months.

“We used a qRT-PCR assay to interrogate circulating tumors cells for AR-FL to seek associations between baseline AR-FL status and PSA [prostate-specific antigen] response rate, PSA progression-free survival, clinical/radiographic progression-free survival, and overall survival,” explained study author Emmanuel S. Antonarakis, associate professor of oncology and urology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.

Higher AR-FL levels correlated with positive AR-V7 detection. The median number of AR-FL copies was 35.5 and 1.4 in AR-V7 positive and AR-V7 negative circulating tumors cells, respectively (P < .001).

Investigators also observed a significant association between AR-FL copy number and PSA₅₀ response, with higher AR-FL levels correlating with lower PSA₅₀ responses (P < .001).

AR-FL level was prognostic for PSA progression-free survival, progression-free survival, and overall survival (P < .001).

“Higher AF-FL levels correlated with inferior clinical outcomes, and generally remained significant in multivariable models,” said Dr Antonarakis. “AR-V7 remained independently prognostic for all outcomes in multivariable analysis.”

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The findings suggest that AR-FL quantification, in addition to AR-V7, could serve as a molecular biomarker of sensitivity to abiraterone and enzalutamide.

Reference

1. Silberstein J, Luber B, Wang H, et al. Clinical significance of AR mRNA quantification from circulating tumor cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone (Abi) or enzalutamide (Enza). Paper presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.