Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer
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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:226351 |
| Acceso en línea: | https://ddd.uab.cat/record/226351 https://dx.doi.org/urn:doi:10.1016/j.eururo.2018.09.049 |
| Access Level: | acceso abierto |
| Palabra clave: | Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker |
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oai:ddd.uab.cat:226351 |
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España |
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Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| title |
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| spellingShingle |
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer Conteduca, Vincenza|||0000-0002-6921-714X Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker |
| title_short |
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| title_full |
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| title_fullStr |
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| title_full_unstemmed |
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| title_sort |
Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| dc.creator.none.fl_str_mv |
Conteduca, Vincenza|||0000-0002-6921-714X Jayaram, Anuradha Romero-Laorden, Nuria Wetterskog, Daniel Salvi, Samanta|||0000-0002-9584-3021 Gurioli, Giorgia Scarpi, Emanuela Castro, Elena|||0000-0002-3691-6454 Marin-Aguilera, Mercedes Lolli, Cristian Schepisi, Giuseppe Maugeri, Antonio Wingate, Anna Farolfi, Alberto Casadio, Valentina Medina, Ana Puente, J|||0000-0002-6910-1331 Vidal, Mª José Méndez Morales-Barrera, Rafael|||0000-0001-7398-0685 Villa-Guzmán, Jose C. Hernando-Polo, Susana Rodriguez-Vida, Alejo|||0000-0002-7304-6857 González-del-Alba, Aránzazu|||0000-0001-6570-009X Mellado, Begoña|||0000-0002-8088-5966 Gonzalez-Billalabeitia, Enrique|||0000-0003-3143-3143 Olmos, David Attard, Gerhardt De Giorgi, Ugo|||0000-0001-7520-2908 |
| author |
Conteduca, Vincenza|||0000-0002-6921-714X |
| author_facet |
Conteduca, Vincenza|||0000-0002-6921-714X Jayaram, Anuradha Romero-Laorden, Nuria Wetterskog, Daniel Salvi, Samanta|||0000-0002-9584-3021 Gurioli, Giorgia Scarpi, Emanuela Castro, Elena|||0000-0002-3691-6454 Marin-Aguilera, Mercedes Lolli, Cristian Schepisi, Giuseppe Maugeri, Antonio Wingate, Anna Farolfi, Alberto Casadio, Valentina Medina, Ana Puente, J|||0000-0002-6910-1331 Vidal, Mª José Méndez Morales-Barrera, Rafael|||0000-0001-7398-0685 Villa-Guzmán, Jose C. Hernando-Polo, Susana Rodriguez-Vida, Alejo|||0000-0002-7304-6857 González-del-Alba, Aránzazu|||0000-0001-6570-009X Mellado, Begoña|||0000-0002-8088-5966 Gonzalez-Billalabeitia, Enrique|||0000-0003-3143-3143 Olmos, David Attard, Gerhardt De Giorgi, Ugo|||0000-0001-7520-2908 |
| author_role |
author |
| author2 |
Jayaram, Anuradha Romero-Laorden, Nuria Wetterskog, Daniel Salvi, Samanta|||0000-0002-9584-3021 Gurioli, Giorgia Scarpi, Emanuela Castro, Elena|||0000-0002-3691-6454 Marin-Aguilera, Mercedes Lolli, Cristian Schepisi, Giuseppe Maugeri, Antonio Wingate, Anna Farolfi, Alberto Casadio, Valentina Medina, Ana Puente, J|||0000-0002-6910-1331 Vidal, Mª José Méndez Morales-Barrera, Rafael|||0000-0001-7398-0685 Villa-Guzmán, Jose C. Hernando-Polo, Susana Rodriguez-Vida, Alejo|||0000-0002-7304-6857 González-del-Alba, Aránzazu|||0000-0001-6570-009X Mellado, Begoña|||0000-0002-8088-5966 Gonzalez-Billalabeitia, Enrique|||0000-0003-3143-3143 Olmos, David Attard, Gerhardt De Giorgi, Ugo|||0000-0001-7520-2908 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker |
| topic |
Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker |
| description |
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-naïve, 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. 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. Analysis of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line therapy showed that plasma androgen receptor (AR)-normal status favored treatment with abiraterone or enzalutamide, whilst docetaxel benefit was unrelated to plasma AR. AR testing in plasma may have clinical utility for treatment selection in mCRPC. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2 2019-01-01 2019 2019-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/226351 https://dx.doi.org/urn:doi:10.1016/j.eururo.2018.09.049 |
| url |
https://ddd.uab.cat/record/226351 https://dx.doi.org/urn:doi:10.1016/j.eururo.2018.09.049 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI16-01565 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-01499 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CM14-00200 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-01226 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-676 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 JCI-2014-19129 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RYC-2015-18625 Ministerio de Educación, Cultura y Deporte https://doi.org/10.13039/501100003176 CAS17-00182 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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Dipòsit Digital de Documents de la UAB |
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1869424053972893696 |
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Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate CancerConteduca, Vincenza|||0000-0002-6921-714XJayaram, AnuradhaRomero-Laorden, NuriaWetterskog, DanielSalvi, Samanta|||0000-0002-9584-3021Gurioli, GiorgiaScarpi, EmanuelaCastro, Elena|||0000-0002-3691-6454Marin-Aguilera, MercedesLolli, CristianSchepisi, GiuseppeMaugeri, AntonioWingate, AnnaFarolfi, AlbertoCasadio, ValentinaMedina, AnaPuente, J|||0000-0002-6910-1331Vidal, Mª José MéndezMorales-Barrera, Rafael|||0000-0001-7398-0685Villa-Guzmán, Jose C.Hernando-Polo, SusanaRodriguez-Vida, Alejo|||0000-0002-7304-6857González-del-Alba, Aránzazu|||0000-0001-6570-009XMellado, Begoña|||0000-0002-8088-5966Gonzalez-Billalabeitia, Enrique|||0000-0003-3143-3143Olmos, DavidAttard, GerhardtDe Giorgi, Ugo|||0000-0001-7520-2908Castration-resistant prostate cancerAndrogen receptorPlasma DNADocetaxelAndrogen receptor-directed therapiesBiomarkerPlasma 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-naïve, 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. 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. Analysis of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line therapy showed that plasma androgen receptor (AR)-normal status favored treatment with abiraterone or enzalutamide, whilst docetaxel benefit was unrelated to plasma AR. AR testing in plasma may have clinical utility for treatment selection in mCRPC.Universitat Autònoma de Barcelona 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/226351https://dx.doi.org/urn:doi:10.1016/j.eururo.2018.09.049reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI16-01565Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-01499Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CM14-00200Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-01226Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-676Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 JCI-2014-19129Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RYC-2015-18625Ministerio de Educación, Cultura y Deporte https://doi.org/10.13039/501100003176 CAS17-00182open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2263512026-06-06T12:50:31Z |
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15,300724 |