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

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.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement G. Attard certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: G. Attard reports receiving commercial research grants from Janssen, Arno Therapeutics, and Innocrin Pharma; has received honoraria and/or travel support from the speakers' bureaus of Janssen, Astellas, Sanofi-Aventis, and Roche/Ventana; has received travel support from Pfizer, Abbott Laboratories, Bayer Healthcare, and Essa Pharmaceuticals; has ownership interest (including patents) in the Institute of Cancer Research Rewards to Inventors; and is a consultant for/advisory board member of Janssen-Cilag, Veridex, Bayer Healthcare, Roche/Ventana, Astellas, Medivation, Pfizer, Novartis, Millennium Pharma, Abbott Laboratories, and Essa Pharma. V. Conteduca, E. Gonzalez-Billalabeitia, and U. De Giorgi received speaker honoraria or travel support from Astellas, Janssen-Cilag, and Sanofi-Aventis. V. Conteduca received consulting fee from Bayer and is an advisory board member of Janssen. E. Castro reports receiving commercial research grants from AstraZeneca, Bayer, Janssen; has received honoraria and/or travel support from the speakers’ bureaus of Astra Zeneca, Astellas, Bayer, Janssen, Pfizer, Bristol Myers Squibb and Roche; and is an advisory board member of Astellas, Bayer and Janssen. N. Romero Laorden has received honoraria and/or travel support from Bayer, Astellas, Janssen-Cilag, and Sanofi-Aventis. D. Olmos has a compensated advisory role for Astellas, AstraZeneca, Bayer, Clovis, Genetech/Roche, Janssen, and uncompensated advisory role for BioOncotech, Tokai; has received a speaker fee from Astellas, Bayer, Janssen, Sanofi, and travel support from Astellas, Bayer, Janssen, Roche; has received research funding (to the institution): AstraZeneca, BioOncotech, Bayer, Janssen. M. Marín-Aguilera has received travel support from Bristol Myers Squibb. Aventis. B. Mellado reports receiving commercial research grants from Roche and Bayer; has received travel support from Pfizer and Janssen; and is a consultant for/advisory board member of Roche, Sanofi, Janssen, Astellas Oncology, Pfizer, Novartis, Bristol Myers Squibb and Ipsen. No potential conflicts of interest were disclosed by other authors.