Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20435
Título
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(es)
Conteduca, Vincenza | Wetterskog, D | Sharabiani, M. T. A | Grande, E | Fernandez-Perez, M. P | Jayaram, A | Salvi, S | Castellano, D | Romanel, A | Lolli, C | Casadio, V | Gurioli, G | Amadori, D | Font, Albert | Vazquez-Estevez, S | Gonzalez del Alba, AranzazuAutor/a del sistema sanitario público de las Islas Baleares Orcid | Mellado, B | Fernandez-Calvo, O | Mendez-Vidal, M. J | Climent, M. A | Duran, Ignacio | Gallardo, E | Rodriguez, A | Santander, C | Saez, M. I | Puente, J | Tandefelt, D. Gasi | Wingate, A | Dearnaley, D | Demichelis, F | De Giorgi, Ugo | Gonzalez-Billalabeitia, E | Attard, G | PREMIERE Collaborators | Spanish Oncology Genitourinary Grp
Fecha de publicación
2017-07
Cita
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.
Idioma
Inglés
Tipo de documento
research article
Resumen
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).
Palabras clave
Castration-resistant prostate cancer | Androgen receptor | Plasma DNA | Enzalutamide | Abiraterone | Biomarker
MESH
Disease-Free Survival | Aged, 80 and over | Disease Progression | Aged | Adult | Humans | Multiplex Polymerase Chain Reaction | DNA Mutational Analysis | Male | Multivariate Analysis | Predictive Value of Tests | Time Factors | Europe | Biomarkers, Tumor | Phenylthiohydantoin | Risk Factors | Kaplan-Meier Estimate | Androstenes | Middle Aged | Circulating Tumor DNA | Prostatic Neoplasms, Castration-Resistant | Prospective Studies | Mutation | Receptors, Androgen | Precision Medicine | Proportional Hazards Models | Treatment Outcome | Antineoplastic Agents, Hormonal | Odds Ratio | Patient Selection
DECS
Antineoplásicos Hormonales | Selección de Paciente | Modelos de Riesgos Proporcionales | Resultado del Tratamiento | Oportunidad Relativa | Europa (Continente) | Análisis Mutacional de ADN | Masculino | Receptores Androgénicos | Persona de Mediana Edad | Estudios Prospectivos | Estimación de Kaplan-Meier | Progresión de la Enfermedad | Medicina de Precisión | Androstenos | Supervivencia sin Enfermedad | Factores de Tiempo | Análisis Multivariante | Neoplasias de la Próstata Resistentes a la Castración | Reacción en Cadena de la Polimerasa Multiplex | Biomarcadores de Tumor | Mutación | Feniltiohidanto�na | Factores de Riesgo | Humanos | Valor Predictivo de las Pruebas | Anciano | Anciano de 80 o más Años | Adulto | ADN Tumoral Circulante
Versión en línea
DOI
Aparece en las colecciones
- Investigación > IIS > IdisBa - Instituto de Investigación Sanitaria Illes Balears (Baleares)
- Investigación > IIS > IDIBAPS - Instituto de Investigaciones Biomédicas August Pi i Sunyer (Cataluña)
- Investigación > IIS > IBIS - Instituto de Biomedicina de Sevilla (Andalucía)
- Investigación > IIS > IMIB - Instituto Murciano de Investigación Biosanitaria Pascual Parrilla (Murcia)
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