دورية أكاديمية
A correlative biomarker study and integrative prognostic model in chemotherapy-naive metastatic castration-resistant prostate cancer treated with enzalutamide
| العنوان: | A correlative biomarker study and integrative prognostic model in chemotherapy-naive metastatic castration-resistant prostate cancer treated with enzalutamide |
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| المؤلفون: | Fernandez-Perez, Maria P, Perez-Navarro, Enrique, Alonso-Gordoa, Teresa, Conteduca, Vicenza, Font, Albert, Vazquez-Estevez, Sergio, Gonzalez-del-Alba, Aranzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S, Mellado, Begona, Fernandez-Calvo, Ovidio, Mendez-Vidal, Maria J, Climent, Miguel A, Duran, Ignacio, Gallardo, Enrique, Rodriguez Sanchez, Angel, Santander, Carmen, Saez, Maria, Puente, Javier, Tudela, Julian, Martinez, Alberto, Lopez-Andreo, Maria J, Padilla, Jose, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, Gonzalez-Billalabeitia, Enrique |
| المصدر: | Prostate , 83 (4) pp. 376-384. (2023) |
| بيانات النشر: | WILEY |
| سنة النشر: | 2023 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, Urology & Nephrology, AR gain, AR-V7, CTCs, enzalutamide, prostate cancer, TMPRSS2-ERG, CIRCULATING TUMOR-CELLS, GENE STATUS, ANDROGEN RECEPTOR, CLINICAL-TRIALS, ABIRATERONE, SURVIVAL, SURROGATE, TMPRSS2, FUSION, MEN |
| 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10164231/1/A%20correlative%20biomarker%20study%20and%20integrative%20prognostic%20model.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10164231Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10164231/1/A%20correlative%20biomarker%20study%20and%20integrative%20prognostic%20model.pdfTest https://discovery.ucl.ac.uk/id/eprint/10164231Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.CA0DB1C2 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |