Plasma androgen receptor copy number status at emergence of metastatic castration-resistant prostate cancer: A pooled multicohort analysis

Anuradha Jayaram, Anna Wingate, Daniel Wetterskog, Vincenza Conteduca, Daniel Khalaf, Mansour Taghavi Azar Sharabiani, Fabio Calabrò, Lorraine Barwell, Susan Feyerabend, Enrique Grande, Alberto Martinez-Carrasco, Albert Font, Alfredo Berruti, Cora N. Sternberg, Rob Jones, Florence Lefresne, Marjolein Lahaye, Shibu Thomas, Shilpy Joshi, Dong ShenDeborah Ricci, Michael Gormley, Axel S. Merseburger, Bertrand Tombal, Matti Annala, Kim N. Chi, Ugo De Giorgi, Enrique Gonzalez-Billalabeitia, Alexander W. Wyatt, Gerhardt Attard*

*Corresponding author for this work
5 Citations (Scopus)


PURPOSE Increases in androgen receptor (AR) copy number (CN) can be detected in plasma DNA when patients develop metastatic castration-resistant prostate cancer. We aim to evaluate the association between AR CN as a continuous variable and clinical outcome. PATIENTS AND METHODS PCR2023 was an international, multi-institution, open-label, phase II study of abiraterone acetate plus prednisolone (AAP) or abiraterone acetate plus dexamethasone that included plasma AR assessment as a predefined exploratory secondary end point. Plasma AR CN data ( identifier: NCT01867710) from this study (n = 133) were pooled with data from the following three other cohorts: Cohort A, which was treated with either AAP or enzalutamide (n = 73); the PREMIERE trial ( identifier: NCT02288936) of biomarkers for enzalutamide (n = 94); and a phase II trial from British Columbia (ClinicalTrials. gov identifier: NCT02125357) that randomly assigned men to either AAP or enzalutamide (n = 201). The primary outcome measures for the biomarker analysis were overall survival and progression-free survival. RESULTS Using multivariable fractional polynomials analysis using Cox regression models, a nonlinear relationship between plasma AR CN and outcome was identified for overall survival, where initially for small incremental gains in CN there was a large added hazard ratio that plateaued at higher CN. The CN cut point associated with the highest local hazard ratio was 1.92. A similar nonlinear association was observed with progression-free survival. In an exploratory analysis of PCR2023, the time from start of long-term androgendeprivation therapy to start of AAP or abiraterone acetate plus dexamethasone was significantly shorter in patients with plasma AR CN of 1.92 or greater than patients with plasma AR CN of less than 1.92 (43 v 130 weeks, respectively; P = .005). This was confirmed in cohort A (P = .003), the PREMIERE cohort (P = .03), and the British Colombia cohort (P = .003). CONCLUSION Patients with metastatic castration-resistant prostate cancer can be dichotomized by a plasma AR CN cut point of 1.92. Plasma AR CN value of 1.92 or greater identifies aggressive disease that is poorly responsive to AR targeting and is associated with a prior short response to primary androgen-deprivation therapy.

Original languageEnglish
JournalJCO Precision Oncology
Publication statusPublished - 24.09.2019

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)


Dive into the research topics of 'Plasma androgen receptor copy number status at emergence of metastatic castration-resistant prostate cancer: A pooled multicohort analysis'. Together they form a unique fingerprint.

Cite this