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

Attard, G; Wetterskog, D; Jayaram, A; Wingate, A; (2019) Plasma AR status and cabazitaxel in heavily-treated metastatic castration-resistant prostate cancer. European Journal of Cancer , 116 pp. 158-168. 10.1016/j.ejca.2019.05.007.

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Abstract

Background Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients 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, pre-therapy 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 PCR 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 14.1months, hazard ratio (HR)=1.44, 95% confidence interval (CI) 0.98-2.13, P=0.064, and PFS 4.0 versus 5.0months, HR=1.47, 95%CI 1.05- 2.07,P=0.024). In mCRPC patients 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 11.5months, HR=1.95, 95%CI 1.13- 3.38,P=0.016), and PFS (2.7 versus 5.0months, 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 are warranted.

Type: Article
Title: Plasma AR status and cabazitaxel in heavily-treated metastatic castration-resistant prostate cancer
DOI: 10.1016/j.ejca.2019.05.007
Publisher version: https://doi.org/10.1016/j.ejca.2019.05.007
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: castration-resistant prostate cancer; androgen receptor; plasma DNA; cabazitaxel; AR directed therapies; biomarker
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10074753
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