PSA provocation by bipolar androgen therapy may predict duration of response to first-line androgen deprivation: Updated results from the BATMAN study.

BACKGROUND

Previously, we reported results from the Phase II BATMAN study (Bipolar Androgen Therapy for Men with Androgen-ablation Naïve prostate cancer). This study (NCT01750398) was designed to evaluate the safety and efficacy of a treatment regimen consisting of a 6-month lead in-phase of androgen deprivation therapy (ADT) followed by alternating 3-month intervals of bipolar androgen therapy (BAT) and ADT alone. Here we report > 5-year follow-up related to the duration of subsequent ADT, response to first-line androgen receptor inhibitors, safety, and survival in men with castration-sensitive prostate cancer treated on the BATMAN study.

METHODS

Univariate Cox regression was utilized to compare overall survival between Responders who achieved a prostate-specific antigen (PSA) level of <4 ng/ml and Non-Responders who achieved a PSA level of ≥4 ng/ml after BAT/ADT. Kaplan-Meier method and Cox regression were used to assess progression-free (PFS) and overall survival (OS) on BAT and on subsequent abiraterone or enzalutamide and on the association between PSA peak during BAT and each time to event outcome.

RESULTS

Over median follow-up of 95 months, the median PFS on ADT for the entire cohort was 47.8. Median OS has not been reached (NR). Median OS for Non-Responders is 43 months versus NR (not reached) for responders (hazard ratio [HR]: 0.176, p = 0.002). Post-BAT, the PSA50 and PSA90 responses to abiraterone or enzalutamide were 94.4% and 66.7%, respectively and median PFS was 20.6 months. Patients with peak PSA level of ≥9 ng/ml after BAT had median PFS of 20.6 months versus NR for those having PSA < 9 ng/ml (HR: 0.122, p < 0.001). Median OS was 79.6 months for patients with PSA peak of ≥9 ng/ml versus NR for those having PSA peak of <9 ng/ml (HR: 0.409, p = 0.131).

CONCLUSION

The use of BAT as part of first-line hormonal therapy strategy does not induce adversely affect long-term survival or induce any significant long-term adverse sequelae in patients with prostate cancer. Cycling BAT may extend the duration of ADT response and enhance response to subsequent androgen ablative therapies. The magnitude of BAT-provoked increase in PSA may predict duration of ADT response and warrants further study.