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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2019 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:226351 |
| Online Access: | https://ddd.uab.cat/record/226351 https://dx.doi.org/urn:doi:10.1016/j.eururo.2018.09.049 |
| Access Level: | Open access |
| Keyword: | Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker |
| _version_ | 1878742148638048256 |
|---|---|
| author | Conteduca, Vincenza|||0000-0002-6921-714X |
| 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 |
| author_browse | Attard, Gerhardt Casadio, Valentina Castro, Elena|||0000-0002-3691-6454 Conteduca, Vincenza|||0000-0002-6921-714X De Giorgi, Ugo|||0000-0001-7520-2908 Farolfi, Alberto Gonzalez-Billalabeitia, Enrique|||0000-0003-3143-3143 González-del-Alba, Aránzazu|||0000-0001-6570-009X Gurioli, Giorgia Hernando-Polo, Susana Jayaram, Anuradha Lolli, Cristian Marin-Aguilera, Mercedes Maugeri, Antonio Medina, Ana Mellado, Begoña|||0000-0002-8088-5966 Morales-Barrera, Rafael|||0000-0001-7398-0685 Olmos, David Puente, J|||0000-0002-6910-1331 Rodriguez-Vida, Alejo|||0000-0002-7304-6857 Romero-Laorden, Nuria Salvi, Samanta|||0000-0002-9584-3021 Scarpi, Emanuela Schepisi, Giuseppe Vidal, Mª José Méndez Villa-Guzmán, Jose C. Wetterskog, Daniel Wingate, Anna |
| 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 |
| collection | Dipòsit Digital de Documents de la UAB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_f0eda54f8fbf56ae2641663cb0bf2d9a |
| institution | Universitat Autònoma de Barcelona |
| instname_str | Universitat Autònoma de Barcelona |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:ddd.uab.cat:226351 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| reponame_str | Dipòsit Digital de Documents de la UAB |
| spelling | Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer 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 Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker 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. https://ddd.uab.cat/record/226351 https://dx.doi.org/urn:doi:10.1016/j.eururo.2018.09.049 |
| 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 | 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_short | Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| title_sort | Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer |
| topic | Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker |
| topic_facet | Castration-resistant prostate cancer Androgen receptor Plasma DNA Docetaxel Androgen receptor-directed therapies Biomarker |
| url | https://ddd.uab.cat/record/226351 https://dx.doi.org/urn:doi:10.1016/j.eururo.2018.09.049 |