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JAMA Oncol. 2018 Sep 1;4(9):1179-1186. doi: 10.1001/jamaoncol.2018.1621.

Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer.

Author information

1
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
2
Department of Medicine, Weill Cornell Medical College, New York, New York.
3
Epic Sciences, San Diego, California.
4
Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.
5
The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
6
Department of Oncology, Western University, London, Ontario, Canada.
7
London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada.
8
Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
9
Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

Abstract

Importance:

A blood test to determine whether to treat patients with metastatic castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling (ARS) inhibitor or taxane is an unmet medical need.

Objective:

To determine whether a validated assay for the nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells can determine differential overall survival among patients with mCRPC treated with taxanes vs ARS inhibitors.

Design, Setting, and Participants:

This blinded correlative study conducted from December 31, 2012, to September 1, 2016, included 142 patients with histologically confirmed mCRPC and who were treated at Memorial Sloan Kettering Cancer Center, The Royal Marsden, or the London Health Sciences Centre. Blood samples were obtained prior to administration of ARS inhibitors or taxanes as a second-line or greater systemic therapy for progressing mCRPC.

Main Outcomes and Measures:

Overall survival after treatment with an ARS inhibitor or taxane in relation to pretherapy AR-V7 status.

Results:

Among the 142 patients in the study (mean [SD] age, 69.5 [9.6] years), 70 were designated as high risk by conventional prognostic factors. In this high-risk group, patients positive for AR-V7 who were treated with taxanes had superior overall survival relative to those treated with ARS inhibitors (median overall survival, 14.3 vs 7.3 months; hazard ratio, 0.62; 95% CI, 0.28-1.39; P = .25). Patients negative for AR-V7 who were treated with ARS inhibitors had superior overall survival relative to those treated with taxanes (median overall survival, 19.8 vs 12.8 months; hazard ratio, 1.67; 95% CI, 1.00-2.81; P = .05).

Conclusions and Relevance:

This study suggests that nuclear-localized AR-V7 protein in circulating tumor cells can identify patients who may live longer with taxane chemotherapy vs ARS inhibitor treatment.

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