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
| Autor: | Conteduca, V, Wetterskog, D, Sharabiani, M. T. A, Grande, Elisabetta, Fernandez Perez, M. P, Jayaram, A, Salvi, S, Castellano, D, Romanel, Alessandro, 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, Demichelis, Francesca, De Giorgi, U, Gonzalez Billalabeitia, E, Attard, G. |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Time Factors plasma DNA Antineoplastic Agents Hormonal DNA Mutational Analysis Kaplan-Meier Estimate urologic and male genital diseases Disease-Free Survival Circulating Tumor DNA abiraterone androgen receptor biomarker castration-resistant prostate cancer enzalutamide Predictive Value of Tests Risk Factors Nitriles Phenylthiohydantoin Biomarkers Tumor Odds Ratio Humans 1112 Oncology and Carcinogenesis Prospective Studies Oncology & Carcinogenesis Precision Medicine Aged Proportional Hazards Models Aged 80 and over Patient Selection Middle Aged Europe Prostatic Neoplasms Castration-Resistant Treatment Outcome Receptors Androgen Benzamides Multivariate Analysis Mutation Disease Progression Androstenes Multiplex Polymerase Chain Reaction |
| Zdroj: | Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| Popis: | 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-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). Results 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 |
| Databáze: | OpenAIRE |
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