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00925njm 22002777a 4500 dc Conteduca, Vincenza author Wetterskog, D author Sharabiani, M. T. A author Grande, E author Fernandez-Perez, M. P author Jayaram, A author Salvi, S author Castellano, D author Romanel, A author Lolli, C author Casadio, V author Gurioli, G author Amadori, D author Font, Albert author Vazquez-Estevez, S author Gonzalez del Alba, AranzazuAutor/a del sistema sanitario público de las Islas Baleares Orcid author Mellado, B author Fernandez-Calvo, O author Mendez-Vidal, M. J author Climent, M. A author Duran, Ignacio author Gallardo, E author Rodriguez, A author Santander, C author Saez, M. I author Puente, J author Tandefelt, D. Gasi author Wingate, A author Dearnaley, D author Demichelis, F author De Giorgi, Ugo author Gonzalez-Billalabeitia, E author Attard, G author PREMIERE Collaborators author Spanish Oncology Genitourinary Grp author 2017-07 Background: 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. Methods: 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-naive and 98 postdocetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naive patients treated with enzalutamide (Secondary cohort; PREMIERE trial). Results: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naive and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P<0.001 and HR 3.81; 95% CI 2.28-6.37; P<0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline >= 50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. ARmutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naive 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<0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P<0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. Conclusion: 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. Clinical Trial number: NCT02288936 (PREMIERE trial). 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;28(7):1508-16. 10.1093/annonc/mdx155 1569-8041 0923-7534 Annals of Oncology http://hdl.handle.net/20.500.13003/9759 28472366 L619392989 2-s2.0-85019315640 http://hdl.handle.net/20.500.12105/20435 404134100016 Castration-resistant prostate cancer Androgen receptor Plasma DNA Enzalutamide Abiraterone Biomarker 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