RT Journal Article
T1 A correlative biomarker study and integrative prognostic model in chemotherapy‐naïve metastatic castration‐resistant prostate cancer treated with enzalutamide
A1 Fernández Perez, María P.
A1 Pérez Navarro, Enrique
A1 Alonso Gordoa, Teresa
A1 Conteduca, Vicenza
A1 Font, Albert
A1 Vázquez Estévez, Sergio
A1 González del Alba, Aránzazu
A1 Wetterskog, Daniel
A1 Antonarakis, Emmanuel S.
A1 Mellado, Begona
A1 Fernández Calvo, Ovidio
A1 Méndez Vidal, María J.
A1 Climent, Miguel A.
A1 Duran, Ignacio
A1 Gallardo, Enrique
A1 Rodriguez Sánchez, Angel
A1 Santander, Carmen
A1 Sáez, Maria I.
A1 Puente, Javier de la
A1 Tudela, Julian
A1 Martínez, Alberto
A1 López Andreo, Maria J.
A1 Padilla, José
A1 Lozano, Rebeca
A1 Hervas, David
A1 Luo, Jun
A1 De Giorgi, Ugo
A1 Castellano Gauna, Daniel Ernesto
A1 Attard, Gerhardt
A1 Grande, Enrique
A1 Gónzalez Billalabeitia, Enrique
AB BackgroundThere is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC).MethodsWe 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.ResultsNinety-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.ConclusionsTMPRSS2-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.
PB Wiley
SN 0270-4137
YR 2023
FD 2023-12-23
LK https://hdl.handle.net/20.500.14352/72991
UL https://hdl.handle.net/20.500.14352/72991
LA eng
NO 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.
NO CRUE-CSIC (Acuerdos Transformativos 2022)
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 19 abr 2025