PD28-04 DETECTION OF ANDROGEN RECEPTOR VARIANT 7 (AR-V7) IN WHOLE BLOOD RNA OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) PATIENTS TREATED WITH ABIRATERONE ACETATE (ABI)

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) I1 Apr 2016PD28-04 DETECTION OF ANDROGEN RECEPTOR VARIANT 7 (AR-V7) IN WHOLE BLOOD RNA OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) PATIENTS TREATED WITH ABIRATERONE ACETATE (ABI) Tilman Todenhöfer, Arun Azad, Jian Gao, Craig Stewart, Bernie Eigl, Arnulf Stenzl, Miriam Teich, Peter Black, Anthony Joshua, and Kim Chi Tilman TodenhöferTilman Todenhöfer More articles by this author , Arun AzadArun Azad More articles by this author , Jian GaoJian Gao More articles by this author , Craig StewartCraig Stewart More articles by this author , Bernie EiglBernie Eigl More articles by this author , Arnulf StenzlArnulf Stenzl More articles by this author , Miriam TeichMiriam Teich More articles by this author , Peter BlackPeter Black More articles by this author , Anthony JoshuaAnthony Joshua More articles by this author , and Kim ChiKim Chi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.391AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Expression of androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) has been associated with resistance to ABI and enzalutamide (ENZ) (Antonarakis et al. N Engl J Med 2014). We have developed a RT-PCR assay that is neither time sensitive nor requires CTC enrichment for detection of prostate cancer (PCa)-associated transcripts in whole blood. Using this assay, our aim was to correlate AR-V7 expression with outcomes on ABI. METHODS 2.5 ml whole blood was collected into PAXgene RNA tubes from mCRPC patients (pts) commencing ABI. RT-PCR was performed for the following genes: AR-V7, FOXA1, GRHL2, HOXB13, KLK2, KLK3 and TMPRSS2:ERG. For each gene, the highest CT value among 20 normal controls was set as the threshold for a positive (+) test. Clinical endpoints were PSA50 response rate (RR) (PSA decline ≥ 50% confirmed ≥ 3 weeks later), PSA30 RR, time to PSA (PCWG2 criteria) or clinical progression (change in anti-cancer therapy or decline in ECOG performance status (PS) ≥ 2 levels due to PCa), and overall survival (OS). RESULTS Whole blood samples were obtained from 37 pts. Median age was 70. 59% received prior docetaxel. All pts were ABI and ENZ naive. PSA50 RR was 37% and PSA30 RR was 48%. Median progression-free survival (PFS) was 3.8 months (mos) and median OS was 21.0 mos. 11% (4/37) of pts were AR-V7+. AR-V7+ pts were more likely to have high ALP (P=0.04), high LDH (P=0.07) and ECOG PS ≥ 2 (P=0.052). Pts with an AR-V7+ test had lower PSA50 RR (0% vs. 42%, P=0.10) and PSA30 RR (0% vs. 52%, P=0.051) together with shorter median PFS (0.7 mos vs. 4.0 mos, P<0.001; log-rank) and median OS (5.5 mos vs. 22.1 mos, P<0.001). Other factors linked with worse OS were high ALP (P=0.02), liver metastases (P=0.03), ≤ 36 mos on primary hormone therapy (P=0.04) and HOXB13+ (P=0.03). CONCLUSIONS RT-PCR detection of AR-V7 transcripts in whole blood was associated with a 0% PSA RR and significantly inferior PFS and OS in pts treated with ABI. These results reinforce the potential utility of AR-V7 as a prognostic and predictive biomarker for mCRPC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e655-e656 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Tilman Todenhöfer More articles by this author Arun Azad More articles by this author Jian Gao More articles by this author Craig Stewart More articles by this author Bernie Eigl More articles by this author Arnulf Stenzl More articles by this author Miriam Teich More articles by this author Peter Black More articles by this author Anthony Joshua More articles by this author Kim Chi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...