2026-06-29T07:22:29Zhttps://docta.ucm.es/rest/oai/requestoai:docta.ucm.es:20.500.14352/729912024-09-24T14:56:44Zcom_20.500.14352_14col_20.500.14352_15
A correlative biomarker study and integrative prognostic model in chemotherapy‐naïve metastatic castration‐resistant prostate cancer treated with enzalutamide
Fernández Perez, María P.
Pérez Navarro, Enrique
Alonso Gordoa, Teresa
Conteduca, Vicenza
Font, Albert
Vázquez Estévez, Sergio
González del Alba, Aránzazu
Wetterskog, Daniel
Antonarakis, Emmanuel S.
Mellado, Begona
Fernández Calvo, Ovidio
Méndez Vidal, María J.
Climent, Miguel A.
Duran, Ignacio
Gallardo, Enrique
Rodriguez Sánchez, Angel
Santander, Carmen
Sáez, Maria I.
Puente, Javier de la
Tudela, Julian
Martínez, Alberto
López Andreo, Maria J.
Padilla, José
Lozano, Rebeca
Hervas, David
Luo, Jun
De Giorgi, Ugo
Castellano Gauna, Daniel Ernesto
Attard, Gerhardt
Grande, Enrique
Gónzalez Billalabeitia, Enrique
AR gain
AR‐V7
CTCs
Enzalutamide
Prostate cancer
TMPRSS2‐ERG
Medicina
Oncología
32 Ciencias Médicas
3201.01 Oncología
CRUE-CSIC (Acuerdos Transformativos 2022)
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 < 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.
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.
Instituto de Salud Carlos III
Depto. de Medicina
Fac. de Medicina
TRUE
pub
2023-06-22T12:39:04Z
2023-06-22T12:39:04Z
2023-12-23
journal article
https://hdl.handle.net/20.500.14352/72991
0270-4137
10.1002/pros.24469
eng
PI18/00883
Fernandez‐Perez MP, Perez‐Navarro E, Alonso‐Gordoa T, Conteduca V, Font A, Vázquez‐Estévez S, et al. A correlative biomarker study and integrative prognostic model in chemotherapy‐naïve metastatic castration‐resistant prostate cancer treated with enzalutamide. The Prostate 2023;83:376–84. https://doi.org/10.1002/pros.24469.
Atribución-NoComercial-SinDerivadas 3.0 España
https://creativecommons.org/licenses/by-nc-nd/3.0/es/
open access
application/pdf
Wiley