Associations between AR-V7 status in circulating tumour cells, circulating tumour cell count and survival in men with metastatic castration-resistant prostate cancer.
Aged
Biomarkers, Tumor
/ blood
Blood Cell Count
Clinical Trials as Topic
/ statistics & numerical data
Follow-Up Studies
Humans
Male
Middle Aged
Neoplasm Metastasis
Neoplastic Cells, Circulating
/ metabolism
Prognosis
Prostatic Neoplasms, Castration-Resistant
/ blood
Protein Isoforms
/ blood
Receptors, Androgen
/ blood
Retrospective Studies
Survival Analysis
Taxoids
/ therapeutic use
AR-V7
Biomarker
Circulating tumour cells
Metastatic castration-resistant prostate cancer
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
31
05
2019
revised:
10
08
2019
accepted:
14
08
2019
pubmed:
23
9
2019
medline:
9
6
2020
entrez:
23
9
2019
Statut:
ppublish
Résumé
The interpretation of the presence of AR-V7 in circulating tumour cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) remains to be elucidated. AR-V7 may hold promise as a predictive biomarker, but there may be prognostic impact of AR-V7 positivity as well. To investigate the clinical value of AR-V7, we determined whether AR-V7 detection in CTCs in patients with mCRPC is associated with CTC counts and survival. Between December 2011 and January 2019, three prospective clinical trials collected clinical data of patients with mCRPC, who progressed after docetaxel and/or enzalutamide or abiraterone. Baseline (and follow-up) blood samples were withdrawn determining CTC count and AR-V7 expression. The majority of patients started cabazitaxel as the next line of treatment after AR-V7 characterisation. A total of 127 samples were evaluable for the analysis of CTC count versus AR-V7 status. Although an association was observed between AR-V7 and CTC count in all patients with mCRPC (p = 0.017), no such association was found in the prognostic unfavourable subgroup of patients with ≥5 CTCs. After adjusting for clinical prognostic factors, AR-V7 expression in CTCs was not associated with overall survival (hazard ratio = 1.33, 95% confidence interval = 0.81-2.15, p = 0.25). We found that AR-V7 expression in CTCs had no additional prognostic value in patients with mCRPC, mostly treated with cabazitaxel. In patients with mCRPC with a predefined worse prognosis of a higher CTC count (≥5), a predictive biomarker is an important unmet medical need. Prospective trials should investigate whether AR-V7 detection in CTCs may guide treatment selection for these adverse prognosis patients.
Sections du résumé
BACKGROUND
The interpretation of the presence of AR-V7 in circulating tumour cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) remains to be elucidated. AR-V7 may hold promise as a predictive biomarker, but there may be prognostic impact of AR-V7 positivity as well. To investigate the clinical value of AR-V7, we determined whether AR-V7 detection in CTCs in patients with mCRPC is associated with CTC counts and survival.
METHODS
Between December 2011 and January 2019, three prospective clinical trials collected clinical data of patients with mCRPC, who progressed after docetaxel and/or enzalutamide or abiraterone. Baseline (and follow-up) blood samples were withdrawn determining CTC count and AR-V7 expression. The majority of patients started cabazitaxel as the next line of treatment after AR-V7 characterisation.
RESULTS
A total of 127 samples were evaluable for the analysis of CTC count versus AR-V7 status. Although an association was observed between AR-V7 and CTC count in all patients with mCRPC (p = 0.017), no such association was found in the prognostic unfavourable subgroup of patients with ≥5 CTCs. After adjusting for clinical prognostic factors, AR-V7 expression in CTCs was not associated with overall survival (hazard ratio = 1.33, 95% confidence interval = 0.81-2.15, p = 0.25).
CONCLUSION
We found that AR-V7 expression in CTCs had no additional prognostic value in patients with mCRPC, mostly treated with cabazitaxel. In patients with mCRPC with a predefined worse prognosis of a higher CTC count (≥5), a predictive biomarker is an important unmet medical need. Prospective trials should investigate whether AR-V7 detection in CTCs may guide treatment selection for these adverse prognosis patients.
Identifiants
pubmed: 31542641
pii: S0959-8049(19)30465-4
doi: 10.1016/j.ejca.2019.08.005
pii:
doi:
Substances chimiques
AR protein, human
0
Biomarkers, Tumor
0
Protein Isoforms
0
Receptors, Androgen
0
Taxoids
0
cabazitaxel
51F690397J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
48-54Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.