141642-159

AR splice variant 7 (AR-V7) and response to taxanes in men with metastatic castration-resistant prostate cancer (mCRPC).

Category: 
Genitourinary Cancer
Session Type and Session Title: 
General Session 2: Evolving Role of Multimodality Treatment in Low-Volume Hormone-Sensitive Metastatic Disease
General Poster Session A: Prostate Cancer
Abstract Number: 

138

Poster Board Number: 
General Poster Session A (Board #A4)
Citation: 
J Clin Oncol 33, 2015 (suppl 7; abstr 138)
Author(s): 
Emmanuel S. Antonarakis, Changxue Lu, Yan Chen, Brandon Luber, Hao Wang, Mary Nakazawa, Angelo M. De Marzo, William B. Isaacs, Rosa Nadal, Channing Judith Paller, Samuel R. Denmeade, Michael Anthony Carducci, Mario A. Eisenberger, Jun Luo; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; The Johns Hopkins Medical Institutions, Baltimore, MD

Abstract Disclosures

Abstract: 

Background: AR-V7 is a truncated form of AR that lacks the ligand-binding domain but remains constitutively active. We previously showed that detection of AR-V7 from circulating tumor cells (CTCs) in men with mCRPC was associated with primary resistance to enzalutamide and abiraterone. Here, we hypothesized that AR-V7[+] patients would retain sensitivity to taxane chemotherapy. Methods: We used a qRT-PCR assay to interrogate CTCs for AR-V7 mRNA in prospectively enrolled patients with mCRPC starting docetaxel or cabazitaxel. We sought associations between AR-V7 status and PSA response rates (the primary endpoint), PSA progression-free survival (PSA-PFS), and clinical/radiographic progression-free survival (PFS). Multivariable regressions were performed to determine the independent effect of AR-V7 status on clinical outcomes. 36 taxane-treated men were required to produce a 2-sided 95% CI for the difference in PSA response rates (between AR-V7[+] and AR-V7[–] men) with an upper bound of 60%, assuming that 30% of men would be AR-V7[+]. Results: 37 taxane-treated patients were enrolled, and 17 (45.9%) had detectable AR-V7 in CTCs. PSA responses were achieved in both AR-V7[+] and AR-V7[–] men (41% vs 65%, P=0.19). Median PSA-PFS was comparable in AR-V7[+] and AR-V7[–] men (4.5 vs 6.2 mo, HR 1.72, P=0.32). Likewise, median PFS was comparable in AR-V7[+] and AR-V7[–] men (5.1 vs 6.9 mo, HR 2.65, P=0.11). After incorporating data from our prior study in 62 abi/enza-treated patients, it was observed that clinical outcomes in AR-V7[+] men were superior with taxanes than with abi/enza, while outcomes did not differ by treatment type in AR-V7[–] men. For example, in AR-V7[+] men, PSA responses were higher in taxane-treated versus abi/enza-treated men (41% vs 0%, P<0.001), and median PSA-PFS and PFS were longer in taxane-treated men (HR for PSA-PFS = 0.19, P=0.001; HR for PFS = 0.21, P=0.003). Conclusions: Detection of AR-V7 in CTCs from men with mCRPC is not associated with primary resistance to taxane chemotherapy, and such patients may retain sensitivity to taxanes. Further, in AR-V7[+] men, taxanes appear to be more efficacious than abi/enza. AR-V7 may represent a treatment-selection marker in mCRPC.