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 PSA50 response (PSA decline ≥50% from baseline) rate at 12-weeks. The primary analysis utilized the entire (intent-to-treat [ITT]) cohort, with those dropping out early counted as non-responders. Secondary/exploratory analyses were in those treated beyond 12-weeks (response-evaluable cohort).
Thirty-six patients enrolled and 6 discontinued prior to response assessment. In the ITT cohort, PSA50 response rate at 12-weeks was 11/36 (31%; 95% CI 17-48%), and 16/36 (44%, 95% CI 28-62%) had a PSA50 response at any time on-study. After a median follow-up of 19 months, the median clinical/radiographic progression-free survival in the ITT cohort was 13.0 months (95% CI 7-17). Clinical outcomes were similar regardless of HRR gene mutational status.
BAT plus olaparib is associated with high response rates and long PFS. Clinical benefit was observed regardless of HRR gene mutational status.
Prostate cancer and prostatic diseases. 2022 Dec 23 [Epub ahead of print]
Michael T Schweizer, Roman Gulati, Todd Yezefski, Heather H Cheng, Elahe Mostaghel, Michael C Haffner, Radhika A Patel, Navonil De Sarkar, Gavin Ha, Ruth Dumpit, Brianna Woo, Aaron Lin, Patrick Panlasigui, Nerina McDonald, Michael Lai, Katie Nega, Jeannette Hammond, Petros Grivas, Andrew Hsieh, Bruce Montgomery, Peter S Nelson, Evan Y Yu
Department of Medicine, University of Washington, Seattle, WA, USA. ., Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Department of Medicine, University of Washington, Seattle, WA, USA., Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.