ASCO 2017: Association of androgen receptor gene status in plasma DNA with outcome on enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer: Exploratory results from the PREMIERE trial—On behalf of SOGUG

Chicago, IL ( Building on previous discoveries studying androgen receptor (AR) status in plasma, and following a road-map for biomarker development, Dr. Grande presented a study aiming to clinically qualify AR status in chemotherapy-naïve metastatic castrate resistant prostate cancer (mCRPC) patients using an optimized multiplex droplet digital PCR (ddPCR) assay (Clinical trial information: NCT02288936).

The PREMIERE trial took place between February and November 2015, including 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC patients from 16 Spanish hospitals. 94 patients had tissue and blood samples acquired at study entry. In this study the authors explored plasma AR correlation to CTC and additional outcomes, including PSA-progression-free survival (sPFS), radiographic progression-free survival (rPFS) and overall survival (OS). 

94 patients had plasma DNA available for analysis. At baseline, AR gain was present in 11 pts (12%) and CTCs in 35 (37%) overall. AR gain in CTC-positive and negative patients was present in 64% and 36%, respectively. At first interim analysis and with a median follow-up of 10.9 months, detection of AR gain was associated with worse sPFS (median, 3.60 versus 15.5 m, HR, 4.33; 95% CI 1.94-9.68; P < 0.001), rPFS (median, 3.90 m versus not reached HR, 8.06; 95% CI, 3.26-19.93; P < 0.001) and OS (medians not reached, HR, 11.08; 95% CI, 2.16-56.95; P = 0.004). These results were independently validated in multivariable analysis including cfDNA and CTCs for all described endpoints. AR gain patients were less likely to have a ≥50% decline in PSA (OR, 4.93; 95% CI, 1.30-18.75; P = 0.025). 

In summary, detection of AR gain in plasma predicts an adverse outcome in chemotherapy-naïve mCRPC. This will need to be further studied in future prospective randomized studies.

Presented By: Enrique Grande, Hospital Universitario Ramón y Cajal, Madrid, Spain

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

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