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

Sarah Q. To, Edmond M. Kwan, Heidi C. Fettke, Andrew Mant, Maria M. Docanto, Luciano Martelotto, Patricia Bukczynska, Nicole Ng, Lisa Jane K. Graham, Phillip Parente, Carmel Pezaro, Kate Mahon, Lisa Horvath, Tilman Todenhöfer, Arun A. Azad

Research output: Contribution to journalArticleResearchpeer-review

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. We designed a whole blood assay for the detection of androgen receptor splice variant (AR-V) 7 and AR-V9. The presence of these AR-Vs does not predict for nonresponse to abiraterone and enzalutamide. Patients should not necessarily be excluded from such therapies if they express these AR-Vs.

Original languageEnglish
Pages (from-to)818-821
Number of pages4
JournalEuropean Urology
Volume73
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

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

Cite this

To, Sarah Q. ; Kwan, Edmond M. ; Fettke, Heidi C. ; Mant, Andrew ; Docanto, Maria M. ; Martelotto, Luciano ; Bukczynska, Patricia ; Ng, Nicole ; Graham, Lisa Jane K. ; Parente, Phillip ; Pezaro, Carmel ; Mahon, Kate ; Horvath, Lisa ; Todenhöfer, Tilman ; Azad, Arun A. / 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. In: European Urology. 2018 ; Vol. 73, No. 6. pp. 818-821.
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title = "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. We designed a whole blood assay for the detection of androgen receptor splice variant (AR-V) 7 and AR-V9. The presence of these AR-Vs does not predict for nonresponse to abiraterone and enzalutamide. Patients should not necessarily be excluded from such therapies if they express these AR-Vs.",
keywords = "Abiraterone, Androgen receptor splice variant, Biomarker, Castration resistant, Enzalutamide, Prostate cancer",
author = "To, {Sarah Q.} and Kwan, {Edmond M.} and Fettke, {Heidi C.} and Andrew Mant and Docanto, {Maria M.} and Luciano Martelotto and Patricia Bukczynska and Nicole Ng and Graham, {Lisa Jane K.} and Phillip Parente and Carmel Pezaro and Kate Mahon and Lisa Horvath and Tilman Todenh{\"o}fer and Azad, {Arun A.}",
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language = "English",
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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. / To, Sarah Q.; Kwan, Edmond M.; Fettke, Heidi C.; Mant, Andrew; Docanto, Maria M.; Martelotto, Luciano; Bukczynska, Patricia; Ng, Nicole; Graham, Lisa Jane K.; Parente, Phillip; Pezaro, Carmel; Mahon, Kate; Horvath, Lisa; Todenhöfer, Tilman; Azad, Arun A.

In: European Urology, Vol. 73, No. 6, 01.06.2018, p. 818-821.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 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

AU - To, Sarah Q.

AU - Kwan, Edmond M.

AU - Fettke, Heidi C.

AU - Mant, Andrew

AU - Docanto, Maria M.

AU - Martelotto, Luciano

AU - Bukczynska, Patricia

AU - Ng, Nicole

AU - Graham, Lisa Jane K.

AU - Parente, Phillip

AU - Pezaro, Carmel

AU - Mahon, Kate

AU - Horvath, Lisa

AU - Todenhöfer, Tilman

AU - Azad, Arun A.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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. We designed a whole blood assay for the detection of androgen receptor splice variant (AR-V) 7 and AR-V9. The presence of these AR-Vs does not predict for nonresponse to abiraterone and enzalutamide. Patients should not necessarily be excluded from such therapies if they express these AR-Vs.

AB - 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. We designed a whole blood assay for the detection of androgen receptor splice variant (AR-V) 7 and AR-V9. The presence of these AR-Vs does not predict for nonresponse to abiraterone and enzalutamide. Patients should not necessarily be excluded from such therapies if they express these AR-Vs.

KW - Abiraterone

KW - Androgen receptor splice variant

KW - Biomarker

KW - Castration resistant

KW - Enzalutamide

KW - Prostate cancer

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DO - 10.1016/j.eururo.2018.01.007

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JO - European Urology

JF - European Urology

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