Dr. Antonarakis on AR-V7 and Resistance to AR-Targeting Agents in mCRPC

Emmanuel S. Antonarakis, MBBCh, assistant professor, Johns Hopkins Medicine, discusses AR-V7 and resistance to AR-targeting agents in men with metastatic castration-resistant prostate cancer (mCRPC).

At the 2014 ESMO Congress, Antonarakis presented overall survival results of both cohorts in a study looking at AR-V7 splice variant and resistance to enzalutamide and abiraterone in mCRPC.

It was found that survival is worse in patients treated with enzalutamide who had AR-V7 detected in their circulating tumor cells compared with those patients who did not have any measurable AR-V7. In patients receiving abiraterone, survival was inferior in patients that were AR-V7-positive compared with those that were AR-V7-negative.

Researchers then conducted a multivariable analysis to adjust for other factors. This model showed that the presence of AR-V7 was an independently worse prognostic factor, and that survival in those patients that were AR-V7-positive was inferior even after appropriate adjustment.

The other factor that was also significant in the multivariable model was whether or not the patient had previously received enzalutamide or abiraterone. In the enzalutamide cohort, Antonarakis says, patients who had previously received abiraterone experienced worse survival. In the abiraterone cohort, those that had received enzalutamide prior — their survival was worse. Those were the only two factors in the multivariable model that portended a worse survival: (1) AR-V7 presence as well as (2) prior treatment with enzalutamide/abiraterone.