Conteduca, V; Jayaram, A; Romero-Laorden, N; Wetterskog, D; Salvi, S; Gurioli, G; Scarpi, E; ... de Giorgi, U; + view all Conteduca, V; Jayaram, A; Romero-Laorden, N; Wetterskog, D; Salvi, S; Gurioli, G; Scarpi, E; Castro, E; Marin-Aguilera, M; Lolli, C; Schepisi, G; Maugeri, A; Wingate, A; Farolfi, A; Casadio, V; Medina, A; Puente, J; Méndez Vidal, MJ; Morales-Barrera, R; Villa-Guzmán, JC; Hernando, S; Rodriguez-Vida, A; González-del-Alba, A; Mellado, B; Gonzalez-Billalabeitia, E; Olmos, D; Attard, G; de Giorgi, U; - view fewer (2019) Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer. European Urology 10.1016/j.eururo.2018.09.049. (In press).

Preview

Text Attard_1-s2.0-S0302283818307395-main.pdf - Published Version Download (1MB) | Preview

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.

Download activity - last month

Export as XMLJSONCSV

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item