The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
Hospital Moinhos de Vento, Porto Alegre, Brazil.
Prostate. 2022 Dec;82(16):1529-1536. doi: 10.1002/pros.24426. Epub 2022 Aug 8.
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.
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.
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).
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.
此前，我们报告了 II 期 BATMAN 研究（双极雄激素治疗雄激素剥夺治疗初治前列腺癌的男性）的结果。该研究（NCT01750398）旨在评估由 6 个月的雄激素剥夺治疗（ADT）导入期和随后的 3 个月双极雄激素治疗（BAT）与 ADT 交替进行的治疗方案的安全性和有效性。在此，我们报告了在 BATMAN 研究中接受治疗的去势敏感性前列腺癌男性的后续 ADT 持续时间、一线雄激素受体抑制剂的反应、安全性和生存的 >5 年随访结果。
使用单变量 Cox 回归比较了 BAT/ADT 后 PSA 水平<4ng/ml 的应答者和 PSA 水平≥4ng/ml 的无应答者的总生存情况。Kaplan-Meier 方法和 Cox 回归用于评估 BAT 和随后的阿比特龙或恩扎鲁胺的无进展生存（PFS）和总生存（OS），以及 BAT 期间 PSA 峰值与每个事件结果之间的关系。
在中位随访 95 个月期间，整个队列的 ADT 中位 PFS 为 47.8 个月。中位 OS 尚未达到（NR）。无应答者的中位 OS 为 43 个月，而应答者的中位 OS 为 NR（未达到）（风险比 [HR]：0.176，p=0.002）。在 BAT 后，阿比特龙或恩扎鲁胺的 PSA50 和 PSA90 反应率分别为 94.4%和 66.7%，中位 PFS 为 20.6 个月。BAT 后 PSA 水平≥9ng/ml 的患者的中位 PFS 为 20.6 个月，而 PSA<9ng/ml 的患者的中位 PFS 为 NR（HR：0.122，p<0.001）。PSA 峰值≥9ng/ml 的患者的中位 OS 为 79.6 个月，而 PSA 峰值<9ng/ml 的患者的中位 OS 为 NR（HR：0.409，p=0.131）。
BAT 作为一线激素治疗策略的一部分使用不会对前列腺癌患者的长期生存或任何显著的长期不良后果产生不利影响。周期性 BAT 可能延长 ADT 反应的持续时间，并增强对随后的雄激素剥夺治疗的反应。BAT 引起的 PSA 增加幅度可能预测 ADT 反应的持续时间，值得进一步研究。
