Faculty Collaboration Database

Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 2023 Mar;26(1):194-200

Date

12/24/2022

Pubmed ID

36564459

Pubmed Central ID

PMC10286318

DOI

10.1038/s41391-022-00636-0

Scopus ID

2-s2.0-85144705758 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

BACKGROUND: 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.

PATIENTS AND METHODS: 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).

RESULTS: 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.

CONCLUSIONS: BAT plus olaparib is associated with high response rates and long PFS. Clinical benefit was observed regardless of HRR gene mutational status.

Author List

Schweizer MT, Gulati R, Yezefski T, Cheng HH, Mostaghel E, Haffner MC, Patel RA, De Sarkar N, Ha G, Dumpit R, Woo B, Lin A, Panlasigui P, McDonald N, Lai M, Nega K, Hammond J, Grivas P, Hsieh A, Montgomery B, Nelson PS, Yu EY

Author

Navonil De Sarkar PhD Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Androgen Antagonists
Androgens
Humans
Male
Nitriles
Prostate-Specific Antigen
Prostatic Neoplasms, Castration-Resistant
Treatment Outcome