Plasma AR status and cabazitaxel in heavily treated metastatic castration-resistant prostate cancer.
AR-directed therapies
Androgen receptor
Biomarker
Cabazitaxel
Castration-resistant prostate cancer
Plasma DNA
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:
07 2019
07 2019
Historique:
received:
12
12
2018
revised:
26
04
2019
accepted:
07
05
2019
pubmed:
15
6
2019
medline:
2
6
2020
entrez:
15
6
2019
Statut:
ppublish
Résumé
Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital polymerase chain reaction was used to identify plasma AR gain and normal samples. The primary objective was to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide. We observed a shorter median overall survival (OS) and progression-free survival (PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) = 1.44, 95% confidence interval [CI] 0.98-2.13, P = 0.064 and PFS 4.0 versus 5.0 months, HR = 1.47, 95% CI 1.05-2.07, P = 0.024). In patients with mCRPC receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR = 1.95, 95% CI 1.13-3.38, P = 0.016) and PFS (2.7 versus 5.0 months, HR = 2.27, 95% CI 1.39-3.71, P = 0.001). Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials is warranted.
Sections du résumé
BACKGROUND
Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown.
PATIENTS AND METHODS
Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital polymerase chain reaction was used to identify plasma AR gain and normal samples. The primary objective was to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide.
RESULTS
We observed a shorter median overall survival (OS) and progression-free survival (PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) = 1.44, 95% confidence interval [CI] 0.98-2.13, P = 0.064 and PFS 4.0 versus 5.0 months, HR = 1.47, 95% CI 1.05-2.07, P = 0.024). In patients with mCRPC receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR = 1.95, 95% CI 1.13-3.38, P = 0.016) and PFS (2.7 versus 5.0 months, HR = 2.27, 95% CI 1.39-3.71, P = 0.001).
CONCLUSION
Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials is warranted.
Identifiants
pubmed: 31200322
pii: S0959-8049(19)30310-7
doi: 10.1016/j.ejca.2019.05.007
pii:
doi:
Substances chimiques
AR protein, human
0
Antineoplastic Agents
0
Biomarkers, Tumor
0
Receptors, Androgen
0
Taxoids
0
cabazitaxel
51F690397J
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-168Subventions
Organisme : Medical Research Council
ID : MR/P002072/1
Pays : United Kingdom
Organisme : Prostate Cancer UK
ID : PG12-49
Pays : United Kingdom
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.