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Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

التفاصيل البيبلوغرافية
العنوان: Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.
المؤلفون: Conteduca, V, Wetterskog, D, Sharabiani, M T A, Grande, E, Fernandez-Perez, M P, Jayaram, A, Salvi, S, Castellano, D, Romanel, A, Lolli, C, Casadio, V, Gurioli, G, Amadori, D, Font, A, Vazquez-Estevez, S, González Del Alba, A, Mellado, B, Fernandez-Calvo, O, Méndez-Vidal, M J, Climent, M A, Duran, I, Gallardo, E, Rodriguez, A, Santander, C, Sáez, M I, Puente, J, Gasi Tandefelt, D, Wingate, A, Dearnaley, D, PREMIERE Collaborators, Spanish Oncology Genitourinary Group, Demichelis, F, De Giorgi, U, Gonzalez-Billalabeitia, E, Attard, G
سنة النشر: 2017
المجموعة: Sistema Sanitario Público de Andalucía (SSPA): Repositorio
مصطلحات موضوعية: abiraterone, androgen receptor, biomarker, castration-resistant prostate cancer, enzalutamide, plasma DNA, Adult, Aged, 80 and over, Androstenes, Antineoplastic Agents, Hormonal, Benzamides, Biomarkers, Tumor, Circulating Tumor DNA, DNA Mutational Analysis, Disease Progression, Disease-Free Survival, Europe, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multiplex Polymerase Chain Reaction, Multivariate Analysis, Mutation, Nitriles, Odds Ratio, Patient Selection
الوصف: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. NCT02288936 ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
ردمك: 978-0-923753-41-2
0-923753-41-9
تدمد: 1569-8041
العلاقة: http://hdl.handle.net/10668/11171Test; PMC5834043; http://www.annalsofoncology.org/article/S0923753419322550/pdfTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834043/pdfTest
DOI: 10.1093/annonc/mdx155
الإتاحة: https://doi.org/10.1093/annonc/mdx155Test
http://hdl.handle.net/10668/11171Test
http://www.annalsofoncology.org/article/S0923753419322550/pdfTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834043/pdfTest
حقوق: Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; open access
رقم الانضمام: edsbas.4D577531
قاعدة البيانات: BASE
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