Extreme bipolar androgen therapy: Alternating darolutamide and testosterone cypionate in patients with metastatic castration-resistant prostate cancer (mCRPC; ExBAT trial/LACOG 0620).

• DOI: 10.1200/jco.2025.43.5_suppl.178
• Publication Date: 2025-02-18T14:32:56Z
• Authors: Pedro Isaacsson; Andrey Soares; Denis Leonardo Fo...; Fernando Cotait M...; Igor Alexandre Pr...; Daniel da Motta G...; Mariane Fontes Dias; Vinicius Carrera ...; Adriano Goncalves...; Rafaela Gomes de ...; Gustavo Werutsky; Taiane Rebelatto; Diogo Assed Bastos

178 Background: Sequencing androgen-receptor signaling inhibitors (ARSi) has limited activity in metastatic castration-resistant prostate cancer (mCRPC). Bipolar Androgen Therapy (BAT), consisting of supraphysiological doses exogenous testosterone, followed by a decline to castrate levels, shown benefit subset patients (pts) with mCRPC, the downregulation AR therapeutic vulnerability which led resensitization ARSi trials. We hypothesize that BAT could significantly enhance efficacy subsequent darolutamide pts who had progressed abiraterone. Methods: The ExBAT/LACOG 0620 ( NCT04558866 ) study is phase II, single-arm, multi-center trial investigating pre-planned regimen alternating and mCRPC after progression on Prior docetaxel for hormone-sensitive disease was allowed. Pts received intramuscular testosterone cypionate 400 mg day 1, oral 1200 mg/day from 29 56, washout period 7 days, 63-day cycles. primary endpoint radiographic progression-free survival (rPFS) at 12 months. Secondary endpoints include median rPFS, PSA50 response, overall (OS), quality life (QoL) safety. Results: From Jun2021 Mar2023, 51 were enrolled 9 centers 48 eligible analysis. Median age 69y (range, 48-92), 23.5% abiraterone castration-sensitive setting 76.5% mCRPC. rPFS rate months 40.9% (95% CI, 26.3 – 55.0) 9.0 3.9 12.9). response 16.7% 7.4–30.2) OS 23.0 17.7 not reached). At cut-off date (22Mar24), 10 remained treatment. QoL maintained during Treatment-related adverse events (TRAEs) rates any grade 3-4 64.7% 9.8% respectively, no 5 TRAE reported. most common AEs bone breast pain. Conclusions: ExBAT demonstrated durable (12 or more) antintumor around 40% pts, manageble safety profile. Further studies evaluating are needed identify biomarkers impact sequencing lines therapy. Clinical information: .