Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/17638
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer
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ISSN: 0302-2838
eISSN: 1873-7560
WOS ID: 000458490100019
Scopus EID: 2-s2.0-85055497223
PMID: 30773204
Embase PUI: L2001222083
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Conteduca, Vincenza; Jayaram, Anuradha; Romero-Laorden, Nuria; Wetterskog, Daniel; Salvi, Samanta; Gurioli, Giorgia; Scarpi, Emanuela; Castro, Elena; Marin-Aguilera, Mercedes; Lolli, Cristian; Schepisi, Giuseppe; Maugeri, Antonio; Wingate, Anna; Farolfi, Alberto; Casadio, Valentina; Medina, Ana; Puente, Javier; Mendez Vidal, Ma Jose; Morales-Barrera, Rafael; Villa-Guzman, Jose C.; Hernando Polo, Susana; Rodriguez-Vida, Alejo; Gonzalez-del-Alba, Aranzazu; Mellado, Begona; Gonzalez-Billalabeitia, Enrique; Olmos, David; Attard, Gerhardt; De Giorgi, UgoPublication date
2019-03Document type
research articleCitation
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.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-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.
Publisher version
https://dx.doi.org/10.1016/j.eururo.2018.09.049Keywords
Castration-resistant prostate cancerAndrogen receptor
Plasma DNA
Docetaxel
Androgen receptor-directed therapies
Biomarker
MeSH
Prostate-Specific AntigenAndrogen Antagonists
Androstenes
Spain
Humans
Antineoplastic Combined Chemotherapy Protocols
Kallikreins
Progression-Free Survival
Antineoplastic Agents
Docetaxel
Prostatic Neoplasms, Castration-Resistant
Male
Time Factors
Receptors, Androgen
Neoplasm Metastasis
Phenylthiohydantoin
DeCS
Supervivencia sin ProgresiónFactores de Tiempo
Neoplasias de la Próstata Resistentes a la Castración
Metástasis de la Neoplasia
Masculino
Feniltiohidantoína
Receptores Androgénicos
Antineoplásicos
Humanos
Calicreínas
Protocolos de Quimioterapia Combinada Antineoplásica
Antígeno Prostático Específico
Androstenos
Antagonistas de Andrógenos
España
Docetaxel
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Hospital Universitario Son Espases - HUSE > Comunicación científicaInstituto de Investigación Sanitaria Islas Baleares - IDISBA > Comunicación científica