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Baseline serum testosterone and differential efficacy of bipolar androgen therapy and enzalutamide in the randomized TRANSFORMER trial

Prostate Cancer and Prostatic Diseases (2024)Cite this article

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Abstract

Bipolar androgen therapy (BAT) is effective in a subset of metastatic castration-resistant prostate cancer (mCRPC) patients. Treatment selection biomarkers are needed due to other therapies that can be equally efficacious. We performed post-hoc analysis to determine whether baseline serum testosterone (T) is a treatment selection marker in the TRANSFORMER study, a randomized trial of abiraterone-pretreated mCRPC patients assigned to BAT (n = 94) or enzalutamide (n = 101). The findings suggest that patients with poor outcomes to abiraterone and serum T ≥ 20 ng/dL may benefit preferentially from BAT over enzalutamide. Baseline testosterone could be considered in the treatment selection process when BAT is an option.

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Fig. 1: Baseline serum T levels stratified by prior Abi duration and Kaplan-Meier curves for clinical or radiological PFS by treatment arms in each subgroup.

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Funding

Supported by a Transformative Grant (W81XWH-14-2-0189) (to S.R.D.) from the Department of Defense Prostate Cancer Research Program. ESA is partially supported by NCI Cancer Center Support Grant P30 CA077598 and DOD grant W81XWH-22-2-0025. MK is partially supported by a Prostate Cancer Foundation Young Investigator Award.

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Authors and Affiliations

  1. Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600N Wolfe St, Baltimore, MD, 21287, USA

    Mayuko Kanayama, Samuel R. Denmeade & Jun Luo

  2. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401N Broadway, Baltimore, MD, 21231, USA

    Hua-Ling Tsai, Hao Wang, Samuel R. Denmeade & Jun Luo

  3. Department of Oncology, Masonic Cancer Center, University of Minnesota Medical Center, 420 Delaware Street SE, MMC 480, Minneapolis, MN, 55455, USA

    Emmanuel S. Antonarakis

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  1. Mayuko Kanayama
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  2. Hua-Ling Tsai
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  3. Hao Wang
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  4. Emmanuel S. Antonarakis
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  5. Samuel R. Denmeade
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  6. Jun Luo
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Contributions

Samuel R Denmeade and Hao Wang had full access to all the data in the study. Jun Luo takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Luo, Antonarakis. Acquisition of data: Samuel R Denmeade and TRANSFORMER investigators. Analysis and interpretation of data: all authors. Drafting of the manuscript: Kanayama, Antonarakis, Luo. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Tsai, Wang. Obtaining funding: Denmeade. Administrative, technical, or material support: Denmeade. Supervision: Luo, Denmeade, Wang, Antonarakis. Other: None.

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Correspondence to Jun Luo.

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Competing interests

All authors declare that they have no conflicts of interest in relation to the article. The authors would like to disclose the following financial relationships that are not related to this article. J Luo has served as a paid consultant/advisor for Sun Pharma. J Luo has received research funding for his institution from Sanofi, Constellation, Calibr, and Cardiff Oncology and is a co-inventor of a technology owned by Johns Hopkins University and licensed to Qiagen and A&G. ES Antonarakis has served as a paid consultant/advisor for Sanofi, Dendreon, Janssen Biotech, ESSA, Merck, AstraZeneca, Clovis Oncology, Lilly, Bayer, and received honorarium from Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA, Astellas Pharma, Merck, AstraZeneca, Clovis Oncology. E Antonarakis received research funding from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, Constellation Pharmaceuticals, as well as travel accommodations from Sanofi, Dendreon, Medivation. E Antonarakis is a co-inventor of a technology owned by Johns Hopkins University and licensed to Qiagen. S Denmeade has Stock and Other Ownership Interests in Sophiris Bio, served as Consultant/advisor for Sophiris Bio, and received travel accommodations from Sophiris Bio.

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Kanayama, M., Tsai, HL., Wang, H. et al. Baseline serum testosterone and differential efficacy of bipolar androgen therapy and enzalutamide in the randomized TRANSFORMER trial. Prostate Cancer Prostatic Dis (2024). https://doi.org/10.1038/s41391-024-00844-w

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  • DOI: https://doi.org/10.1038/s41391-024-00844-w

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