ASCO 2017: Association of androgen receptor status in plasma DNA with outcome on enzalutamide or abiraterone or castration resistant prostate cancer

Chicago, IL (UroToday.com) There is an urgent need to identify biomarkers to guide personalized therapy in castrate-resistant prostate cancer (CRPC). Dr. Vincenza Conteduca presented a study aiming to clinically qualify the association of androgen receptor (AR) status in plasma DNA with worse outcome in pre- and post-docetaxel (doc) CRPC.  

The authors used droplet digital (dd) PCR to assess AR copy number (CN) and mutations (2105T > A (p.L702H) and 2632A > G (p.T878A) status in plasma DNA from 171 patients treated with abiraterone (abi)/enzalutamide (enza) in biomarker protocols at 2 institutions. The aim was to evaluate plasma AR after sample collection but prior to analysis.  

We first optimized multiplex ddPCR to accurately define AR status and identified an AR CN cutpoint = 2.01 as having the greatest likelihood to split patients into 2 prognostic groups. We confirmed a strong agreement between ddPCR and NGS for quantitating AR CN and mutation allelic frequency (Bland-Altman test: mean difference -0.02 95%CI -2.45 to 2.41; mean difference -0.01 95%CI -0.015 to 0.016 respectively). AR CN gain was observed in 10 (14%) pre- and 33 (34%) post-doc patients and associated with a worse overall survival (OS) (HR 3.98 95%CI 1.74-9.10 p < 0.001; HR 3.81 95%CI 2.28-6.37 p < 0.001 respectively), progression-free survival (PFS) (HR 2.18 95%CI 1.08-4.39 p = 0.03; HR 1.95 95%CI 1.23-3.11 p = 0.01 respectively) and PSA decline ≥50% (OR 4.7 95%CI 1.17-19.17 p = 0.035; OR 5.0 95%CI 1.70-14.91 p = 0.003 respectively). AR mutations were observed in 8 (11%) post-doc, but no pre-doc abi-treated patients and also associated with worse OS (HR 3.26 95%CI 1.47-not reached p = 0.004). There was no interaction between AR and doc status (p = 0.83 for OS, p = 0.99 for PFS). Multivariable analysis, adjusting for AR CN and mutations, previous doc, double stranded DNA concentration, LDH, confirmed AR status was independently associated with OS (HR 3.77 95%CI 2.42-5.88 p < 0.001 and HR 2.76 95%CI 1.26-6.07 p = 0.011 for AR CN and mutation respectively) and PFS (HR 1.96 95% CI 1.32-2.93 p = 0.001). 

In summary, plasma AR status assessment using multiplex ddPCR identifies CRPC with worse outcome to enza/abi in pre-/post-doc CRPC. Additional clinical qualification is available from the PREMIERE study. Prospective evaluation of treatment decisions based on plasma AR is now required.

Presented By: Vincenza Conteduca, MD, PhD, Centre for Evolution and Cancer, The Institute of Cancer Research, London SW7 3RP, UK, London, United Kingdom

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA





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