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Repisalud author Conteduca, Vincenza author Jayaram, Anuradha author Romero-Laorden, Nuria author Wetterskog, Daniel author Salvi, Samanta author Gurioli, Giorgia author Scarpi, Emanuela author Castro, Elena author Marin-Aguilera, Mercedes author Lolli, Cristian author Schepisi, Giuseppe author Maugeri, Antonio author Wingate, Anna author Farolfi, Alberto author Casadio, Valentina author Medina, Ana author Puente, Javier author Mendez Vidal, María Jose author Morales-Barrera, Rafael author Villa-Guzman, Jose C author Hernando Polo, Susana author Rodriguez-Vida, Alejo author Gonzalez-del-Alba, Aranzazu author Mellado, Begona author Gonzalez-Billalabeitia, Enrique author Olmos, David author Attard, Gerhardt author De Giorgi, Ugo 2024-09-10T13:07:08Z 2024-09-10T13:07:08Z 2019-03 Conteduca V, Jayaram A, Romero-Laorden N, Wetterskog D, Salvi S, Gurioli G, et al. Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer. Eur Urol. 2019 Mar;75(3):368-73. Epub 2018 Oct 26. 10.1016/j.eururo.2018.09.049 1873-7560 0302-2838 European Urology http://hdl.handle.net/20.500.13003/17638 30773204 L2001222083 2-s2.0-85055497223 https://hdl.handle.net/20.500.12105/22692 458490100019 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. eng Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer research article