dc.contributor.author | Conteduca, Vincenza | |
dc.contributor.author | Wetterskog, D | |
dc.contributor.author | Sharabiani, M. T. A | |
dc.contributor.author | Grande, E | |
dc.contributor.author | Fernandez-Perez, M. P | |
dc.contributor.author | Jayaram, A | |
dc.contributor.author | Salvi, S | |
dc.contributor.author | Castellano, D | |
dc.contributor.author | Romanel, A | |
dc.contributor.author | Lolli, C | |
dc.contributor.author | Casadio, V | |
dc.contributor.author | Gurioli, G | |
dc.contributor.author | Amadori, D | |
dc.contributor.author | Font, Albert | |
dc.contributor.author | Vazquez-Estevez, S | |
dc.contributor.author | Gonzalez del Alba, AranzazuAutor/a del sistema sanitario público de las Islas Baleares Orcid | |
dc.contributor.author | Mellado, B | |
dc.contributor.author | Fernandez-Calvo, O | |
dc.contributor.author | Mendez-Vidal, M. J | |
dc.contributor.author | Climent, M. A | |
dc.contributor.author | Duran, Ignacio | |
dc.contributor.author | Gallardo, E | |
dc.contributor.author | Rodriguez, A | |
dc.contributor.author | Santander, C | |
dc.contributor.author | Saez, M. I | |
dc.contributor.author | Puente, J | |
dc.contributor.author | Tandefelt, D. Gasi | |
dc.contributor.author | Wingate, A | |
dc.contributor.author | Dearnaley, D | |
dc.contributor.author | Demichelis, F | |
dc.contributor.author | De Giorgi, Ugo | |
dc.contributor.author | Gonzalez-Billalabeitia, E | |
dc.contributor.author | Attard, G | |
dc.contributor.author | PREMIERE Collaborators | |
dc.contributor.author | Spanish Oncology Genitourinary Grp | |
dc.date.accessioned | 2024-07-11T09:10:34Z | |
dc.date.available | 2024-07-11T09:10:34Z | |
dc.date.issued | 2017-07 | |
dc.identifier.citation | 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. | en |
dc.identifier.issn | 0923-7534 | |
dc.identifier.other | http://hdl.handle.net/20.500.13003/9759 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20435 | |
dc.description.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-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). | en |
dc.description.sponsorship | This work was funded by Prostate Cancer UK (PG12-49) and Cancer Research UK (A13239) and was supported by the NIHR Royal Marsden and the Institute of Cancer Research (ICR) Biomedical Research Centre. VC was funded by a European Society of Medical Oncology Translational Clinical Research Fellowship, AJ by an Irish Health Research Board Clinical Research Fellowship and a Medical Research Council Clinical Research Fellowship, DGT by a European Union Marie Curie Intra-European Postdoctoral Fellowship, EG by Instituto de Salud Carlos III and the Spanish Society of Medical Oncology (SEOM)/Chris Foundation (no grant numbers apply) and GA by a Cancer Research UK Advanced Clinician Scientist Fellowship. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The PREMIERE trial was sponsored by Spanish Genito-Urinary oncology Group that received a grant from Astellas to support the conduct of the trial. | es_ES |
dc.language.iso | eng | en |
dc.publisher | Oxford University Press | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Castration-resistant prostate cancer | |
dc.subject | Androgen receptor | |
dc.subject | Plasma DNA | |
dc.subject | Enzalutamide | |
dc.subject | Abiraterone | |
dc.subject | Biomarker | |
dc.subject.mesh | Disease-Free Survival | * |
dc.subject.mesh | Aged, 80 and over | * |
dc.subject.mesh | Disease Progression | * |
dc.subject.mesh | Aged | * |
dc.subject.mesh | Adult | * |
dc.subject.mesh | Humans | * |
dc.subject.mesh | Multiplex Polymerase Chain Reaction | * |
dc.subject.mesh | DNA Mutational Analysis | * |
dc.subject.mesh | Male | * |
dc.subject.mesh | Multivariate Analysis | * |
dc.subject.mesh | Predictive Value of Tests | * |
dc.subject.mesh | Time Factors | * |
dc.subject.mesh | Europe | * |
dc.subject.mesh | Biomarkers, Tumor | * |
dc.subject.mesh | Phenylthiohydantoin | * |
dc.subject.mesh | Risk Factors | * |
dc.subject.mesh | Kaplan-Meier Estimate | * |
dc.subject.mesh | Androstenes | * |
dc.subject.mesh | Middle Aged | * |
dc.subject.mesh | Circulating Tumor DNA | * |
dc.subject.mesh | Prostatic Neoplasms, Castration-Resistant | * |
dc.subject.mesh | Prospective Studies | * |
dc.subject.mesh | Mutation | * |
dc.subject.mesh | Receptors, Androgen | * |
dc.subject.mesh | Precision Medicine | * |
dc.subject.mesh | Proportional Hazards Models | * |
dc.subject.mesh | Treatment Outcome | * |
dc.subject.mesh | Antineoplastic Agents, Hormonal | * |
dc.subject.mesh | Odds Ratio | * |
dc.subject.mesh | Patient Selection | * |
dc.title | 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 | en |
dc.type | research article | en |
dc.rights.license | Attribution 4.0 International | * |
dc.identifier.pubmedID | 28472366 | es_ES |
dc.format.volume | 28 | es_ES |
dc.format.number | 7 | es_ES |
dc.format.page | 1508-1516 | es_ES |
dc.identifier.doi | 10.1093/annonc/mdx155 | |
dc.identifier.e-issn | 1569-8041 | es_ES |
dc.relation.publisherversion | https://dx.doi.org/10.1093/annonc/mdx155 | en |
dc.identifier.journal | Annals of Oncology | es_ES |
dc.rights.accessRights | open access | en |
dc.subject.decs | Antineoplásicos Hormonales | * |
dc.subject.decs | Selección de Paciente | * |
dc.subject.decs | Modelos de Riesgos Proporcionales | * |
dc.subject.decs | Resultado del Tratamiento | * |
dc.subject.decs | Oportunidad Relativa | * |
dc.subject.decs | Europa (Continente) | * |
dc.subject.decs | Análisis Mutacional de ADN | * |
dc.subject.decs | Masculino | * |
dc.subject.decs | Receptores Androgénicos | * |
dc.subject.decs | Persona de Mediana Edad | * |
dc.subject.decs | Estudios Prospectivos | * |
dc.subject.decs | Estimación de Kaplan-Meier | * |
dc.subject.decs | Progresión de la Enfermedad | * |
dc.subject.decs | Medicina de Precisión | * |
dc.subject.decs | Androstenos | * |
dc.subject.decs | Supervivencia sin Enfermedad | * |
dc.subject.decs | Factores de Tiempo | * |
dc.subject.decs | Análisis Multivariante | * |
dc.subject.decs | Neoplasias de la Próstata Resistentes a la Castración | * |
dc.subject.decs | Reacción en Cadena de la Polimerasa Multiplex | * |
dc.subject.decs | Biomarcadores de Tumor | * |
dc.subject.decs | Mutación | * |
dc.subject.decs | Feniltiohidanto�na | * |
dc.subject.decs | Factores de Riesgo | * |
dc.subject.decs | Humanos | * |
dc.subject.decs | Valor Predictivo de las Pruebas | * |
dc.subject.decs | Anciano | * |
dc.subject.decs | Anciano de 80 o más Años | * |
dc.subject.decs | Adulto | * |
dc.subject.decs | ADN Tumoral Circulante | * |
dc.identifier.scopus | 2-s2.0-85019315640 | |
dc.identifier.wos | 404134100016 | |
dc.identifier.pui | L619392989 | |