A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide
Fernandez-Perez, María P. (Hospital General Universitario Morales Meseguer (Múrcia))
Perez-Navarro, Enrique (Hospital Universitario 12 de Octubre (Madrid))
Alonso-Gordoa, Teresa (Hospital Universitario Ramón y Cajal (Madrid))
Conteduca, Vincenza (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) "Dino Amadori" IRCCS)
Font, Albert (Institut Català d'Oncologia)
Vázquez-Estévez, Sergio (H. Universitario Lucus Augusti)
González-del-Alba, Aránzazu (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Wetterskog, Daniel (Paul O'Gorman Building)
Antonarakis, Emmanuel S. (Johns Hopkins University School of Medicine)
Mellado, Begoña (Hospital Clínic i Provincial de Barcelona)
Fernandez-Calvo, Ovidio (Complejo Hospitalario Universitario Ourense)
Méndez-Vidal, María J. (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Climent, Miguel Ángel (Fundació Institut Valencià d'Oncologia)
Duran, Ignacio (Instituto de Biomedicina de Sevilla)
Gallardo, Enrique (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Rodriguez Sanchez, Angel (Hospital Universitario de León)
Santander, Carmen (Hospital Universitario Miguel Servet (Saragossa))
Sáez, Maria I. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Puente, Javier (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Tudela, Julian (Hospital General Universitario Morales Meseguer (Múrcia))
Martínez, Alberto (Biobanco de la región de Murcia)
López-Andreo, Maria J. (SAI-IMIB-Universidad de Murcia)
Padilla, José (Hospital General Universitario Morales Meseguer (Múrcia))
Lozano, Rebeca (Instituto de Investigación Biomédica de Málaga)
Hervas, David (Instituto de Investigación Sanitaria La Fe)
Luo, Jun (Johns Hopkins University School of Medicine)
De Giorgi, Ugo (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) "Dino Amadori" IRCCS)
Castellano, Daniel (Hospital Universitario 12 de Octubre (Madrid))
Attard, Gerhardt (Paul O'Gorman Building)
Grande, Enrique (MD Anderson Cancer Center Madrid)
Gonzalez-Billalabeitia, Enrique (Universidad Católica San Antonio de Murcia-UCAM)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). 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. 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. 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.
Ajuts:	Ministerio de Economía y Competitividad BA16/00038 Instituto de Salud Carlos III PI18/00883
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	AR gain ; AR-V7 ; CTCs ; Enzalutamide ; Prostate cancer ; TMPRSS2-ERG
Publicat a:	The Prostate, Vol. 83 (december 2022) , ISSN 1097-0045

DOI: 10.1002/pros.24469
PMID: 36564933

9 p, 1.2 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d’Investigació i Innovació Parc Taulí (I3PT)
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