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Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer

Conteduca, V; Jayaram, A; Romero-Laorden, N; Wetterskog, D; Salvi, S; Gurioli, G; Scarpi, E; ... de Giorgi, U; + view all (2019) Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer. European Urology 10.1016/j.eururo.2018.09.049. (In press). Green open access

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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 exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institution study was a pooled analysis of AR status, determined by droplet digital PCR, on pre-treatment 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 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), nor PSA response [odds ratio (OR)=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 7 chemotherapy-naïve, abiraterone/enzalutamide-treated patients with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR=0.27,95%CI=0.11-0.68, p=0.005) and PFS (HR=0.28, 95%CI=0.12-0.64, p=0.002). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal (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 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.

Type: Article
Title: Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.eururo.2018.09.049
Publisher version: https://doi.org/10.1016/j.eururo.2018.09.049
Language: English
Additional information: © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: castration-resistant prostate cancer; androgen receptor; plasma DNA; docetaxel; AR directed therapies; biomarker
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/10056909
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