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Eur Urol. 2018 Jun;73(6):818-821. doi: 10.1016/j.eururo.2018.01.007.

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.

Author information

1
Department of Medicine, School of Clinical Sciences, Monash University, Australia.
2
Department of Medicine, School of Clinical Sciences, Monash University, Australia; Department of Medical Oncology, Monash Health, Australia.
3
Medical Oncology Unit, Eastern Health, Australia.
4
Department of Medical Oncology, Monash Health, Australia.
5
Medical Oncology, Chris O'Brien Lifehouse, Australia.
6
Medical Oncology Unit, Eastern Health, Australia; Eastern Health Clinical School, Monash University, Australia.
7
Medical Oncology, Chris O'Brien Lifehouse, Australia; Garvan Institute of Medical Research, Australia.
8
Medical Oncology, Chris O'Brien Lifehouse, Australia; Garvan Institute of Medical Research, Australia; Royal Prince Alfred Hospital, Australia; University of Sydney, Australia.
9
Department of Urology, Eberhard-Karls-University Tuebingen, Germany.
10
Department of Medicine, School of Clinical Sciences, Monash University, Australia; Department of Medical Oncology, Monash Health, Australia. Electronic address: arun.azad@monash.edu.

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.

KEYWORDS:

Abiraterone; Androgen receptor splice variant; Biomarker; Castration resistant; Enzalutamide; Prostate cancer

PMID:
29398263
DOI:
10.1016/j.eururo.2018.01.007
[Indexed for MEDLINE]

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