Plasma androgen receptor and response to adapted and standard docetaxel regimen in castration-resistant prostate cancer : A multicenter biomarker study

Copyright © 2021 Elsevier Ltd. All rights reserved..

BACKGROUND: Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown.

PATIENTS AND METHODS: This was a multi-institution study of associations between baseline plasma AR copy number status, assessed by droplet digital PCR, and outcome in 325 mCRPC patients receiving docetaxel at standard or adapted regimen at the discretion of the treating physician. Upon analysis, patients were assigned randomly to either a training (n = 217) or validation (n = 108) cohort.

RESULTS: In the training cohort, AR-gained patients treated with adapted docetaxel regimen had a significantly worse median progression-free survival (PFS) (3.8 vs 6.3 months, hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.34-4.95, p < 0.0001), median overall survival (10.8 vs 20.6 months, HR 1.98, 95% CI 1.09-3.62, p = 0.0064) and PSA response (PSA > -50%: odds ratio 4.88 95%CI 1.55-14.32, p = 0.013) as compared to plasma AR normal patients. These findings were all confirmed in the validation cohort. However, in patients treated with standard docetaxel regimen, these differences were not seen. The interaction between AR CN status and dose reduction of docetaxel was considered as independent factor for PFS in both the training and validation cohort (HR 2.84, 95% CI 1.41-5.73, p = 0.003, and HR 4.79, 95% CI 1.79-12.82, p = 0.002).

CONCLUSION: Despite the retrospective non-randomised design of this study, our hypothesis-generating findings could suggest plasma AR as a potential biomarker for optimal docetaxel timing and dose in mCRPC patients. Prospective trials are warranted.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:152

Enthalten in:

European journal of cancer (Oxford, England : 1990) - 152(2021) vom: 28. Juli, Seite 49-59

Sprache:

Englisch

Beteiligte Personen:

Conteduca, Vincenza [VerfasserIn]
Wetterskog, Daniel [VerfasserIn]
Castro, Elena [VerfasserIn]
Scarpi, Emanuela [VerfasserIn]
Romero-Laorden, Nuria [VerfasserIn]
Gurioli, Giorgia [VerfasserIn]
Jayaram, Anuradha [VerfasserIn]
Lolli, Cristian [VerfasserIn]
Schepisi, Giuseppe [VerfasserIn]
Wingate, Anna [VerfasserIn]
Casadei, Chiara [VerfasserIn]
Lozano, Rebeca [VerfasserIn]
Brighi, Nicole [VerfasserIn]
Aragón, Isabel M [VerfasserIn]
Marin-Aguilera, Mercedes [VerfasserIn]
Gonzalez-Billalabeitia, Enrique [VerfasserIn]
Mellado, Begoña [VerfasserIn]
Olmos, David [VerfasserIn]
Attard, Gerhardt [VerfasserIn]
De Giorgi, Ugo [VerfasserIn]

Links:

Volltext

Themen:

15H5577CQD
AR protein, human
Androgen receptor
Biomarker
Biomarkers, Tumor
Castration-resistant prostate cancer
Docetaxel
Dose modulation
Journal Article
Multicenter Study
Plasma DNA
Prednisone
Receptors, Androgen
Research Support, Non-U.S. Gov't
VB0R961HZT
Validation Study

Anmerkungen:

Date Completed 10.11.2021

Date Revised 10.02.2022

published: Print-Electronic

ClinicalTrials.gov: NCT03381326

Citation Status MEDLINE

doi:

10.1016/j.ejca.2021.04.025

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM326262350