ExBAT Trial Shows Promise in Metastatic Castrate-Resistant Prostate Cancer Treatment
The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium in San Francisco, CA, highlighted new advancements in prostate cancer treatment. One notable study presented by Dr. Pedro Isaacsson Velho from Hospital Moinhos de Vento in Porto Alegre, Brazil, focused on a novel therapy known as extreme bipolar androgen therapy (BAT).
Understanding Androgen Receptor Therapeutic Resistance
Androgen receptor inhibition remains the primary treatment for advanced prostate cancer. However, patients almost universally develop resistance to this therapy. Prostate cancer cells adapt to low testosterone levels by increasing androgen receptor activity, which can lead to castration resistance. This same adaptation makes the cells vulnerable to high levels of testosterone, thus creating an opportunity for innovative treatments like BAT.
What is Bipolar Androgen Therapy (BAT)?
BAT involves rapidly alternating between high and low testosterone levels. Traditionally, this was achieved using testosterone cypionate, a medication administered every 28 days, combined with continuous testosterone suppression through castration or hormone-blocking drugs. Dr. Velho and his team proposed that BAT could enhance the effectiveness of androgen receptor pathway inhibitors (ARPIs), such as darolutamide, particularly in patients who had progressed on abiraterone acetate therapy.
Study Design and Objectives
The ExBAT study was a single-arm, multicenter, phase II trial designed to evaluate the effectiveness of alternating BAT and darolutamide in mCRPC patients. Patients enrolled in the study were required to have disease progression after abiraterone acetate and had to provide tumor tissue samples for molecular analysis. The treatment regimen consisted of intramuscular testosterone cypionate 400 mg on day 1, followed by 1,200 mg of oral darolutamide daily from day 29 to 56, with a one-week washout period before repeating the cycle every 63 days.
The primary endpoint was radiographic progression-free survival (rPFS) at 12 months. Secondary endpoints included median rPFS, PSA50 response rate, overall survival, quality of life, and safety profile.
Enrollment and Patient Characteristics
Between June 2021 and March 2023, 51 patients were recruited across nine centers. Forty-eight of these patients were eligible for efficacy analysis. The average age of participants was 70 years old. About 78% of patients had received abiraterone in a castrate-resistant setting, with the remaining 22% receiving it in a castrate-sensitive context.
Results and Implications
Dr. Velho reported that the ExBAT trial demonstrated significant anti-tumor activity in approximately 40% of patients who had previously progressed on abiraterone acetate therapy. This durable (≥12 months) response suggests that alternating BAT and darolutamide could be a promising addition to the treatment arsenal for mCRPC.
The safety profile of the regimen was manageable. While more research is needed, these results indicate that BAT has the potential to identify biomarkers of response and assess its impact on ARPI sequencing in subsequent treatments.
Conclusion
The ExBAT study represents a step forward in understanding how to treat metastatic castrate-resistant prostate cancer. By exploiting the paradoxical vulnerability of prostate cancer cells to high testosterone levels, this therapy opens up new avenues for treatment. However, further investigation is crucial to fully understand its potential and to identify patients who are most likely to benefit from it.
As the field of oncology continues to evolve, stay tuned for more updates on innovative treatments and breakthroughs. We welcome your comments and feedback on this study and its implications for prostate cancer management.
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