Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer

Bipolar androgen therapy (BAT) results in rapid fluctuation of testosterone (T) between near-castrate and supraphysiological levels and has shown promise in metastatic castration-resistant prostate cancer (mCRPC). Its clinical effects may be mediated through induction of DNA damage, and preclinical studies suggest synergy with PARP inhibitors.This was a single-center, Phase II trial testing olaparib plus BAT (T cypionate/enanthate 400 mg every 28 days) with ongoing androgen deprivation. Planned recruitment was 30 subjects (equal proportions with/without homologous recombination repair [HRR] gene mutations) with mCRPC post abiraterone and/or enzalutamide. The primary objective was to determine PSAThirty-six patients enrolled and 6 discontinued prior to response assessment. In the ITT cohort, PSABAT plus olaparib is associated with high response rates and long PFS. Clinical benefit was observed regardless of HRR gene mutational status.