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A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide.

Authors :
Fernandez-Perez MP
Perez-Navarro E
Alonso-Gordoa T
Conteduca V
Font A
Vázquez-Estévez S
González-Del-Alba A
Wetterskog D
Antonarakis ES
Mellado B
Fernandez-Calvo O
Méndez-Vidal MJ
Climent MA
Duran I
Gallardo E
Rodriguez Sanchez A
Santander C
Sáez MI
Puente J
Tudela J
Martínez A
López-Andreo MJ
Padilla J
Lozano R
Hervas D
Luo J
de Giorgi U
Castellano D
Attard G
Grande E
Gonzalez-Billalabeitia E
Source :
The Prostate [Prostate] 2023 Mar; Vol. 83 (4), pp. 376-384. Date of Electronic Publication: 2022 Dec 23.
Publication Year :
2023

Abstract

Background: There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC).<br />Methods: We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical-molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort.<br />Results: Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort.<br />Conclusions: TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers.<br /> (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1097-0045
Volume :
83
Issue :
4
Database :
MEDLINE
Journal :
The Prostate
Publication Type :
Academic Journal
Accession number :
36564933
Full Text :
https://doi.org/10.1002/pros.24469