RT Journal Article
T1 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.
A1 Conteduca, V
A1 Wetterskog, D
A1 Sharabiani, M T A
A1 Grande, E
A1 Fernandez-Perez, M P
A1 Jayaram, A
A1 Salvi, S
A1 Castellano, D
A1 Romanel, A
A1 Lolli, C
A1 Casadio, V
A1 Gurioli, G
A1 Amadori, D
A1 Font, A
A1 Vazquez-Estevez, S
A1 Gonzalez Del Alba, A
A1 Mellado, B
A1 Fernandez-Calvo, O
A1 Méndez-Vidal, M J
A1 Climent, M A
A1 Duran, I
A1 Gallardo, E
A1 Rodriguez, A
A1 Santander, C
A1 Saez, M I
A1 Puente, J
A1 Gasi Tandefelt, D
A1 Wingate, A
A1 Dearnaley, D
A1 Demichelis, F
A1 De Giorgi, U
A1 Gonzalez-Billalabeitia, E
A1 Attard, G
K1 Abiraterone
K1 Androgen receptor
K1 Biomarker
K1 Castration-resistant prostate cancer
K1 Enzalutamide
K1 Plasma DNA
AB 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. 
PB Elsevier
YR 2017
FD 2017-05-03
LK http://hdl.handle.net/10668/11171
UL http://hdl.handle.net/10668/11171
LA en
NO Conteduca V, Wetterskog D, Sharabiani MTA, Grande E, Fernandez-Perez MP, Jayaram A, et al. 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. Ann Oncol. 2017 Jul 1;28(7):1508-1516
DS RISalud
RD Apr 9, 2025