Resensitization of Prostate Cancer With Bipolar Androgen Therapy
Posted: Wednesday, July 1, 2020
Bipolar androgen therapy (BAT) may be more effective at resensitizing metastatic castration-resistant prostate cancer to direct androgen receptor antagonists than abiraterone. This mode of therapy consists of driving testosterone levels to the supraphysiologic range, followed by a return to near-castrate levels of 28-day treatment cycles. In addition, the presence of AR-V7 (androgen receptor splice variant 7 messenger RNA) seemed to predict a worse outcome with BAT and rechallenge with enzalutamide or abiraterone. These findings were presented during the ASCO20 Virtual Scientific Program by Mark Christopher Markowski, MD, PhD, of Johns Hopkins University, Baltimore (Abstract 5576).
The study enrolled 59 patients with prostate cancer whose last therapy was either abiraterone (n = 29) or enzalutamide (n = 30). Patients received at least one dose of 400mg BAT intramuscularly every 28 days. After clinical or radiographic progression on BAT, patients were re-challenged with the androgen receptor targeted therapy to which they were most recently resistant.
Of the patients who were previously on abiraterone, 5 achieved a 50% decline in prostate specific antigen (PSA) from baseline after BAT. In addition, 9 patients in the enzalutamide group achieved a 50% reduction in PSA. The objective response rate for the abiraterone group was 28.6% and was 50% in the enzalutamide group.
After re-challenging patients with abiraterone (n = 19) or enzalutamide (n = 22), 15.8% and 68.2% of patients had their PSA levels decline by 50%, respectively. The total duration of benefit (PFS2) for these patients (defined by the progression free survival on BAT plus the progression free survival on re-challenge) was significantly longer in the post-enzalutamide patients as compared to the post-abiraterone patients. The PFS2 was 12.75 months in the enzalutamide group and was 8.125 months in the abiraterone group.
Disclosure: For full authors’ disclosures, visit coi.asco.org.
