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Expression of androgen receptor splice variant 7 or 9 in whole blood does not predict response to androgen-axis-targeting agents in metastatic castration-resistant prostate cancer

Abstract

In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response. To further investigate, we designed a highly sensitive and specific whole blood assay for detecting AR-V7 and AR-V9. We then examined for a correlation between baseline AR-V7/V9 status and treatment outcome in 37 mCRPC patients commencing abiraterone or enzalutamide. Of the patients, 24% (9/37) were AR-V-positive. Notably, prostate-specific antigen (PSA) response rates did not significantly differ between AR-V-positive (6/9) and AR-V-negative (18/28) patients (66% vs 64%, p=0.9). Likewise, median PSA progression-free survival was not significantly different between AR-V-positive and AR-V-negative patients (9.2 mo vs not reached; p=0.9). These data, which support the findings of the pivotal ARMOR3-SV clinical trial, suggest that baseline AR-V expression does not predict outcomes in mCRPC patients receiving abiraterone or enzalutamide. PATIENT SUMMARY: Detection of androgen receptor splice variants (AR-Vs) in circulating tumour cells of advanced prostate cancer patients has been linked to resistance to abiraterone and enzalutamide. We designed a blood test to detect AR-Vs that can be performed more routinely than tests involving circulating tumour cells and found that patients with AR-Vs still benefit from these effective treatments.

Type Journal
ISBN 1873-7560 (Electronic) 0302-2838 (Linking)
Authors To, S. Q.; Kwan, E. M.; Fettke, H. C.; Mant, A.; Docanto, M. M.; Martelotto, L.; Bukczynska, P.; Ng, N.; Graham, L. K.; Parente, P.; Pezaro, C.; Mahon, K.; Horvath, L.; Todenhofer, T.; Azad, A. A.
Responsible Garvan Author Prof Lisa Horvath
Publisher Name EUROPEAN UROLOGY
Published Date 2018-06-01
Published Volume 73
Published Issue 6
Published Pages 818-821
Status Published in-print
DOI 10.1016/j.eururo.2018.01.007
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/29398263