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
Conteduca, V. (Centre for Evolution and Cancer. The Institute of Cancer Research, London)
Wetterskog, D. (Centre for Evolution and Cancer. The Institute of Cancer Research, London)
Sharabiani (Royal Marsden NHS Foundation Trust. Research Data Management and Statistics Unit)
Grande, E. (Hospital Ramon y Cajal. Departamento de Oncologia Médica)
Fernandez Perez, M. P. (Hospital Universitario Morales Meseguer. Departamento de Hematologia y de Oncologia Médica)
Jayaram, A. (Centre for Evolution and Cancer. The Institute of Cancer Research, London)
Salvi, S. (Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS)
Castellano, D. (Hospital Universitario 12 de Octubre. Departamento de Oncologia Médica)
Romanel, A. (Università di Trento. Centro di Biologia Integrata)
Lolli, C. (Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS)
Casadio, V. (Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS)
Gurioli, G. (Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS)
Amadori, D. (Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS)
Font, A. (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vazquez Estevez, S. (, Hospital Universitario Lucus Augusti. Departamento de Oncologia Médica)
González del Alba, A. (Hospital Universitario Son Espases Mallorca. Departament d'Oncologia Médica)
Mellado, B. (IDIBAPS Hospital Clinic. Departament d'Oncologia Médica)
Fernandez Calvo, O. (Hospital de Ourense. Departamento de Oncologia Médica)
Méndez Vidal, M. J. (Hospital Universitario Reina Sofía. Departamento de Oncologia Médica)
Climent, M. A. (Instituto Valenciano de Oncología)
Duran, I. (Instituto de Biomedicina de Sevilla)
Gallardo, E. (Hospital Universitari Parc Taulí. Departament d'Oncologia Médica)
Rodriguez, A. (Hospital de León. Departamento de Oncologia Médica)
Santander, C. (Hospital Universitario Miguel Servet. Departamento de Oncologia Médica)
Sáez, M. I. (Hospital Regional y Hospital Virgen de la Victoria, Malaga. Departamento de Oncologia Médica)
Puente, J. (Hospital Clínico San Carlos. Departamento de Oncologia Médica)
Gasi Tandefelt, D. (Centre for Evolution and Cancer. The Institute of Cancer Research, London)
Wingate, A. (Centre for Evolution and Cancer. The Institute of Cancer Research, London)
Dearnaley, D. (Royal Marsden NHS Foundation Trust. Academic Urology Unit)
Demichelis, F. (Università di Trento. Centro di Biologia Integrata)
De Giorgi, U. (Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS)
Gonzalez Billalabeitia, E. (Hospital Universitario Morales Meseguer. Departamento de Hematologia y de Oncologia Médica)
Attard, G. (Centre for Evolution and Cancer. The Institute of Cancer Research, London)
Spanish Oncology Genitourinary Group
Universitat Autònoma de Barcelona

Date: 2017
Abstract: 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 postdocetaxel 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<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; P¼0. 03, and HR 1. 95; 95% CI 1. 23–3. 11; P¼0. 01, respectively) and rate of PSA decline50% [odds ratio (OR), 4. 7; 95% CI 1. 17–19. 17; P¼0. 035 and OR, 5. 0; 95% CI 1. 70–14. 91; P¼0. 003, respectively]. ARmutations [2105T>A (p. L702H) and 520 3_ $a 2632A>G (p. T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naı¨ve abiraterone-treated patients and were also associated with worse OS (HR 3. 26; 95% CI 1. 47–not reached; P¼0. 004). There was no interaction between AR and docetaxel status (P¼0. 83 for OS, P¼0. 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; P¼0. 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).
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Castration-resistant prostate cancer ; Androgen receptor ; Plasma DNA ; Enzalutamide ; Abiraterone ; Biomarker
Published in: Annals of Oncology, Núm. 28 (2017) , p. 1508-1516



9 p, 341.6 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2018-10-17, last modified 2019-07-17



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