A Potential Biomarker for Resistance to Prostate Cancer Drugs

Robert Dreicer, MD, MS, FACP

Presence of the androgen receptor splice variant 7 in circulating tumor cells was associated with resistance to enzalutamide and abiraterone.

Extensive clinical experience and recent reports from retrospective studies provide compelling evidence of both de novo and acquired resistance to abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer. Although both agents have significant activity in the disease, no data informs the clinician a priori of the potential utility of these agents for individual patients.

To predict response or resistance to enzalutamide or abiraterone in this setting, investigators prospectively evaluated whether presence of the androgen receptor (AR) splice variant 7 (AR-V7) in circulating tumor cells affects prostate-specific antigen (PSA) response, clinical or radiographic progression, and both progression-free and overall survival.

A total of 62 patients received therapy with enzalutamide or abiraterone, of whom 39% and 19%, respectively, had detectable AR-V7 in circulating tumor cells. Regardless of the drug used, men whose tumors were AR-V7 positive had lower PSA response and shorter time to PSA progression as well as shorter clinical or radiographic progression-free survival. For patients in both groups, overall survival was shorter in men with detectable versus undetectable AR-V7 at baseline. No AR-V7–positive patient had meaningful clinical benefit from enzalutamide or abiraterone therapy.

Citation(s):

Antonarakis ES et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014 Sep 3; [e-pub ahead of print].

Nelson PS.Targeting the androgen receptor in prostate cancer — A resilient foe. N Engl J Med 2014 Sep 3; [e-pub ahead of print].