دورية أكاديمية
A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide
| العنوان: | A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide |
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| المؤلفون: | Fernández-Pérez, M. P., Pérez-Navarro, Enrique, Alonso Gordoa, Teresa, Conteduca, Vicenza, Font Pous, Albert, Vázquez-Estévez, Sergio, González del Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado González, Begoña, Fernández-Calvo, Ovidio, Méndez-Vidal, María J., Climent, Miguel A., Durán, Ignacio, Gallardo, Enrique, Rodríguez Sánchez, Ángel, Santander, Carmen, Sáez, María Isabel, Puente Vázquez, Javier, Tudela, Julián, Martínez, Alberto, López-Andreo, María J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, García-Castellanos, Daniel, Attard, Gerhardt, Grande, Enrique, González-Billalabeitia, E. |
| المساهمون: | Astellas Pharma, Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Fundación CRIS contra el Cáncer |
| بيانات النشر: | John Wiley & Sons |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Prostate cancer, AR gain, AR-V7, CTCs, TMPRSS2-ERG, Enzalutamide |
| الوصف: | [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. ; The authors would like to acknowledge all the staff at SOGUG for their support to run the PREMIERE trial, Astellas for supporting this research, ISCIII from the Spanish Ministry of Health, and Cris Cancer Foundation for their support. This trial was ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0270-4137 1097-0045 |
| العلاقة: | Publisher's version; The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1002/pros.24469; https://doi.org/10.1002/pros.24469Test; Sí; The Prostate 83(4): 376-384 (2023); http://hdl.handle.net/10261/333013Test; http://dx.doi.org/10.13039/501100004948Test; http://dx.doi.org/10.13039/501100003751Test; http://dx.doi.org/10.13039/501100004587Test; 2-s2.0-85145039209; https://api.elsevier.com/content/abstract/scopus_id/85145039209Test |
| DOI: | 10.1002/pros.24469 |
| DOI: | 10.13039/501100004948 |
| DOI: | 10.13039/501100003751 |
| DOI: | 10.13039/501100004587 |
| الإتاحة: | https://doi.org/10.1002/pros.2446910.13039/50110000494810.13039/50110000375110.13039/501100004587Test http://hdl.handle.net/10261/333013Test https://api.elsevier.com/content/abstract/scopus_id/85145039209Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.80EB7BB5 |
| قاعدة البيانات: | BASE |
| تدمد: | 02704137 10970045 |
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| DOI: | 10.1002/pros.24469 |