Prostate cancer (PC) becomes resistant to chronic castration via an adaptive increase in androgen receptor (AR) axis activity. AR overexpression, however, is a liability that can be exploited therapeutically through rapid cycling between high supraphysiologic and low castrate levels of serum testosterone (T), (Bipolar Androgen Therapy (BAT)). In a pilot study, 14 men with CRPC treated with BAT showed a 50% PSA and objective response. A larger study was initiated in which asymptomatic men with CRPC and progression on abiraterone (A) and/or enzalutamide (E) (30/cohort) receive T cypionate 400 mg every 28 days. At BAT progression men are rechallenged with A or E. Co-primary endpoints include PSA response after 3 cycles of BAT and after re-treatment of E or A. To date, 37 have completed ≥3 cycles of BAT: 11/37 (30%) had ≥ 50% PSA decline. 4/17 (23%) had RECIST responses. Post-BAT, 8/25 (32%) had ≥ 50% PSA response to retreatment A or E. Six men were AR-V7+ and all became AR-V7 negative after BAT with 2/6 having PSA response. BAT has generally been well tolerated with no DLTs thus far. 1 patient had a self-limited increase in pain and 1 had urinary retention, otherwise there were no bone/soft tissue AEs with BAT to suggest disease flare. This preliminary data demonstrates the safety and activity of BAT in patients with CRPC post-A and/or E with PSA and objective responses, including responses in AR-V7+ men. An ongoing multi-center randomized trial is testing BAT vs E in the post-A CRPC population.
Funding: One-in-Six Foundation, NIH, Department of Defense Prostate Cancer Research Program.
Presenting Author: Samuel R. Denmeade, M.D. Department of Oncology, The Johns Hopkins University School of Medicine, Cancer Research Building 1, 1650 Orleans Street, Baltimore, Maryland, USA. Email: firstname.lastname@example.org.