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

Background There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration‐resistant prostate cancer (CRPC). Methods We conducted a phase II trial of enzalutamide in first‐line chemo‐naïve asymptomatic or minimally symptomatic mCRPC and...

Full description

Saved in:
Bibliographic Details
Published in:The Prostate 2023-03, Vol.83 (4), p.376-384
Main Authors: Fernandez‐Perez, María P., Perez‐Navarro, Enrique, Alonso‐Gordoa, Teresa, Conteduca, Vicenza, Font, Albert, Vázquez‐Estévez, Sergio, González‐del‐Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado, Begona, Fernandez‐Calvo, Ovidio, Méndez‐Vidal, María J., Climent, Miguel A., Duran, Ignacio, Gallardo, Enrique, Rodriguez Sanchez, Angel, Santander, Carmen, Sáez, Maria I., Puente, Javier, Tudela, Julian, Martínez, Alberto, López‐Andreo, Maria J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, Gonzalez‐Billalabeitia, Enrique
Format: Article
Language:English
Subjects:
Alkaline phosphatase
Alternative splicing
Androgen receptors
Androgens
AR gain
AR‐V7
Biomarkers
Biomarkers, Tumor - genetics
Castration
Chemotherapy
Copy number
CTCs
enzalutamide
Fusion protein
Humans
Male
Metastases
Neoplastic Cells, Circulating - pathology
Nitriles - therapeutic use
Original
Patients
Plasma
Prognosis
Prostate cancer
Prostate-Specific Antigen
Prostatic Neoplasms, Castration-Resistant - drug therapy
Prostatic Neoplasms, Castration-Resistant - genetics
Prostatic Neoplasms, Castration-Resistant - pathology
Receptors, Androgen - genetics
TMPRSS2‐ERG
Tumor cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration‐resistant prostate cancer (CRPC). 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. 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 
ISSN:0270-4137
1097-0045
DOI:10.1002/pros.24469