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 Journal Article


Authors: Scher, H. I.; Graf, R. P.; Schreiber, N. A.; Jayaram, A.; Winquist, E.; McLaughlin, B.; Lu, D.; Fleisher, M.; Orr, S.; Lowes, L.; Anderson, A.; Wang, Y.; Dittamore, R.; Allan, A. L.; Attard, G.; Heller, G.
Article Title: 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
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. © 2018 American Medical Association. All rights reserved.
Journal Title: JAMA Oncology
Volume: 4
Issue: 9
ISSN: 2374-2437
Publisher: American Medical Association  
Date Published: 2018-09-01
Start Page: 1179
End Page: 1186
Language: English
DOI: 10.1001/jamaoncol.2018.1621
PROVIDER: scopus
PMCID: PMC6139066
PUBMED: 29955787
DOI/URL:
Notes: Article -- Export Date: 1 October 2018 -- Source: Scopus
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MSK Authors
  1. Glenn Heller
    295 Heller
  2. Martin Fleisher
    237 Fleisher
  3. Howard Scher
    817 Scher