Plasma AR status and cabazitaxel in heavily treated metastatic castration-resistant prostate cancer

Vincenza Conteduca, Elena Castro, Daniel Wetterskog, Emanuela Scarpi, Anuradha Jayaram, Nuria Romero-Laorden, David Olmos, Giorgia Gurioli, Cristian Lolli, Maria Isabel Sáez, Javier Puente, Giuseppe Schepisi, Samanta Salvi, Anna Wingate, Ana Medina, Rosa Querol-Niñerola, Mercedes Marin-Aguilera, Jose Angel Arranz, Giuseppe Fornarini, Umberto BassoBegoña Mellado, Enrique Gonzalez-Billalabeitia, Gerhardt Attard, Ugo De Giorgi

Research output: Contribution to journalArticle

Abstract

Background: Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. Patients and methods: Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital polymerase chain reaction was used to identify plasma AR gain and normal samples. The primary objective was to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide. Results: We observed a shorter median overall survival (OS) and progression-free survival (PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) = 1.44, 95% confidence interval [CI] 0.98–2.13, P = 0.064 and PFS 4.0 versus 5.0 months, HR = 1.47, 95% CI 1.05–2.07, P = 0.024). In patients with mCRPC receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR = 1.95, 95% CI 1.13–3.38, P = 0.016) and PFS (2.7 versus 5.0 months, HR = 2.27, 95% CI 1.39–3.71, P = 0.001). Conclusion: Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials is warranted.

Original languageEnglish
Pages (from-to)158-168
Number of pages11
JournalEuropean Journal of Cancer
Volume116
DOIs
Publication statusPublished - Jul 1 2019

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Castration
Androgen Receptors
Prostatic Neoplasms
docetaxel
Disease-Free Survival
Confidence Intervals
Survival
cabazitaxel
Therapeutics
Biomarkers

Keywords

  • Androgen receptor
  • AR-directed therapies
  • Biomarker
  • Cabazitaxel
  • Castration-resistant prostate cancer
  • Plasma DNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Plasma AR status and cabazitaxel in heavily treated metastatic castration-resistant prostate cancer. / Conteduca, Vincenza; Castro, Elena; Wetterskog, Daniel; Scarpi, Emanuela; Jayaram, Anuradha; Romero-Laorden, Nuria; Olmos, David; Gurioli, Giorgia; Lolli, Cristian; Sáez, Maria Isabel; Puente, Javier; Schepisi, Giuseppe; Salvi, Samanta; Wingate, Anna; Medina, Ana; Querol-Niñerola, Rosa; Marin-Aguilera, Mercedes; Arranz, Jose Angel; Fornarini, Giuseppe; Basso, Umberto; Mellado, Begoña; Gonzalez-Billalabeitia, Enrique; Attard, Gerhardt; De Giorgi, Ugo.

In: European Journal of Cancer, Vol. 116, 01.07.2019, p. 158-168.

Research output: Contribution to journalArticle

Conteduca, V, Castro, E, Wetterskog, D, Scarpi, E, Jayaram, A, Romero-Laorden, N, Olmos, D, Gurioli, G, Lolli, C, Sáez, MI, Puente, J, Schepisi, G, Salvi, S, Wingate, A, Medina, A, Querol-Niñerola, R, Marin-Aguilera, M, Arranz, JA, Fornarini, G, Basso, U, Mellado, B, Gonzalez-Billalabeitia, E, Attard, G & De Giorgi, U 2019, 'Plasma AR status and cabazitaxel in heavily treated metastatic castration-resistant prostate cancer', European Journal of Cancer, vol. 116, pp. 158-168. https://doi.org/10.1016/j.ejca.2019.05.007
Conteduca, Vincenza ; Castro, Elena ; Wetterskog, Daniel ; Scarpi, Emanuela ; Jayaram, Anuradha ; Romero-Laorden, Nuria ; Olmos, David ; Gurioli, Giorgia ; Lolli, Cristian ; Sáez, Maria Isabel ; Puente, Javier ; Schepisi, Giuseppe ; Salvi, Samanta ; Wingate, Anna ; Medina, Ana ; Querol-Niñerola, Rosa ; Marin-Aguilera, Mercedes ; Arranz, Jose Angel ; Fornarini, Giuseppe ; Basso, Umberto ; Mellado, Begoña ; Gonzalez-Billalabeitia, Enrique ; Attard, Gerhardt ; De Giorgi, Ugo. / Plasma AR status and cabazitaxel in heavily treated metastatic castration-resistant prostate cancer. In: European Journal of Cancer. 2019 ; Vol. 116. pp. 158-168.
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T1 - Plasma AR status and cabazitaxel in heavily treated metastatic castration-resistant prostate cancer

AU - Conteduca, Vincenza

AU - Castro, Elena

AU - Wetterskog, Daniel

AU - Scarpi, Emanuela

AU - Jayaram, Anuradha

AU - Romero-Laorden, Nuria

AU - Olmos, David

AU - Gurioli, Giorgia

AU - Lolli, Cristian

AU - Sáez, Maria Isabel

AU - Puente, Javier

AU - Schepisi, Giuseppe

AU - Salvi, Samanta

AU - Wingate, Anna

AU - Medina, Ana

AU - Querol-Niñerola, Rosa

AU - Marin-Aguilera, Mercedes

AU - Arranz, Jose Angel

AU - Fornarini, Giuseppe

AU - Basso, Umberto

AU - Mellado, Begoña

AU - Gonzalez-Billalabeitia, Enrique

AU - Attard, Gerhardt

AU - De Giorgi, Ugo

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. Patients and methods: Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital polymerase chain reaction was used to identify plasma AR gain and normal samples. The primary objective was to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide. Results: We observed a shorter median overall survival (OS) and progression-free survival (PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) = 1.44, 95% confidence interval [CI] 0.98–2.13, P = 0.064 and PFS 4.0 versus 5.0 months, HR = 1.47, 95% CI 1.05–2.07, P = 0.024). In patients with mCRPC receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR = 1.95, 95% CI 1.13–3.38, P = 0.016) and PFS (2.7 versus 5.0 months, HR = 2.27, 95% CI 1.39–3.71, P = 0.001). Conclusion: Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials is warranted.

AB - Background: Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. Patients and methods: Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital polymerase chain reaction was used to identify plasma AR gain and normal samples. The primary objective was to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide. Results: We observed a shorter median overall survival (OS) and progression-free survival (PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) = 1.44, 95% confidence interval [CI] 0.98–2.13, P = 0.064 and PFS 4.0 versus 5.0 months, HR = 1.47, 95% CI 1.05–2.07, P = 0.024). In patients with mCRPC receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR = 1.95, 95% CI 1.13–3.38, P = 0.016) and PFS (2.7 versus 5.0 months, HR = 2.27, 95% CI 1.39–3.71, P = 0.001). Conclusion: Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials is warranted.

KW - Androgen receptor

KW - AR-directed therapies

KW - Biomarker

KW - Cabazitaxel

KW - Castration-resistant prostate cancer

KW - Plasma DNA

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