期刊
EUROPEAN UROLOGY
卷 75, 期 3, 页码 368-373出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.eururo.2018.09.049
关键词
Castration-resistant prostate cancer; Androgen receptor; Plasma DNA; Docetaxel; Androgen receptor-directed therapies; Biomarker
资金
- European Society of Medical Oncology Translational Clinical Research Fellowship
- Medical Research Council [MR/P002072/1]
- Cancer Research UK Advanced Clinician Scientist Grant [A22744]
- Prostate Cancer UK [PG12-49]
- Instituto de Salud Carlos III (ISCII) [PI16/01565]
- Instituto de Salud Carlos III (ISCIII) [PI15/01499]
- Instituto de Salud Carlos III [CM14-00200]
- Prostate Cancer Foundation Young Investigator Award (2017)
- Ministerio de Economia, Industria y Competitividad [JCI-2014-19129, RYC-2015-18625]
- Instituto de Salud Carlos III-Subdireccion General de Evaluacion y Fomento de la Investigacion [PI12/01226, PI15/676]
- European Regional Development Fund
- CERCA Programme/Generalitat de Catalunya
- Ministerio de Educacion, Cultura y Deportes [CAS17/00182]
- MRC [MR/P002072/1, MR/P002072/2] Funding Source: UKRI
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-naive, 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. Patient summary: 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. (C) 2018 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.
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