%0 Journal Article
%A Fernández Perez, María P.
%A Pérez Navarro, Enrique
%A Alonso Gordoa, Teresa
%A Conteduca, Vicenza
%A Font, Albert
%A Vázquez Estévez, Sergio
%A González del Alba, Aránzazu
%A Wetterskog, Daniel
%A Antonarakis, Emmanuel S.
%A Mellado, Begona
%A Fernández Calvo, Ovidio
%A Méndez Vidal, María J.
%A Climent, Miguel A.
%A Duran, Ignacio
%A Gallardo, Enrique
%A Rodriguez Sánchez, Angel
%A Santander, Carmen
%A Sáez, Maria I.
%A Puente, Javier de la
%A Tudela, Julian
%A Martínez, Alberto
%A López Andreo, Maria J.
%A Padilla, José
%A Lozano, Rebeca
%A Hervas, David
%A Luo, Jun
%A De Giorgi, Ugo
%A Castellano Gauna, Daniel Ernesto
%A Attard, Gerhardt
%A Grande, Enrique
%A Gónzalez Billalabeitia, Enrique
%T A correlative biomarker study and integrative prognostic model in chemotherapy‐naïve metastatic castration‐resistant prostate cancer treated with enzalutamide
%D 2023
%@ 0270-4137
%U https://hdl.handle.net/20.500.14352/72991
%X 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.
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