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| Home > Articles > Published articles > Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
(Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori) (Hospital Universitario Quirón, Madrid) (Vall d'Hebron Institut d'Oncologia) (Hospital del Mar (Barcelona, Catalunya)) (Hospital Universitari Son Espases (Palma de Mallorca, Balears)) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Hospital General Universitario Morales Meseguer (Múrcia))| Date: | 2019 |
| Abstract: | Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in case of AR gain (hazard ratio [HR] = 1. 61, 95% confidence interval [CI] = 1. 08-2. 39, p = 0. 018), but not PFS (HR = 1. 04, 95% CI 0. 74-1. 46, p = 0. 8) or PSA response (odds ratio = 1. 14, 95% CI = 0. 65-1. 99, p = 0. 7). We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 73 chemotherapy-naïve, abiraterone/enzalutamide-treated patients, with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC patients receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR = 0. 16, 95% CI = 0. 06-0. 46, p < 0. 001) and PFS (HR = 0. 31, 95% CI = 0. 12-0. 80, p = 0. 02). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR -normal patients (HR = 1. 93, 95% CI = 1. 19-3. 12, p = 0. 008) and a suggestion favoring docetaxel for AR -gained patients (HR = 0. 53, 95% CI = 0. 24-1. 16, p = 0. 11). These data suggest that AR -normal patients should receive abiraterone/enzalutamide and AR -gained could benefit from docetaxel. This treatment selection merits prospective evaluation in a randomized trial. We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR -gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker. Analysis of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line therapy showed that plasma androgen receptor (AR)-normal status favored treatment with abiraterone or enzalutamide, whilst docetaxel benefit was unrelated to plasma AR. AR testing in plasma may have clinical utility for treatment selection in mCRPC. |
| Grants: | Instituto de Salud Carlos III PI16-01565 Instituto de Salud Carlos III PI15-01499 Instituto de Salud Carlos III CM14-00200 Instituto de Salud Carlos III PI12-01226 Instituto de Salud Carlos III PI15-676 Ministerio de Economía y Competitividad JCI-2014-19129 Ministerio de Economía y Competitividad RYC-2015-18625 Ministerio de Educación, Cultura y Deporte CAS17-00182 |
| 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.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Castration-resistant prostate cancer ; Androgen receptor ; Plasma DNA ; Docetaxel ; Androgen receptor-directed therapies ; Biomarker |
| Published in: | European Urology, Vol. 75 (march 2019) , p. 368-373, ISSN 1873-7560 |
