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Clin Genitourin Cancer. 2017 Aug;15(4):463-471. doi: 10.1016/j.clgc.2016.10.006. Epub 2016 Oct 27.

Efficacy of Therapies After Galeterone in Patients With Castration-resistant Prostate Cancer.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address: Rmckay5@partners.org.
2
Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
4
Clinical Operations and Program Management, Tokai Pharmaceuticals, Cambridge, MA.
5
Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
6
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
7
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA.

Abstract

BACKGROUND:

Galeterone is a multi-targeted agent with activity as a CYP17 inhibitor, androgen receptor antagonist, and also causes androgen receptor degradation. It has shown meaningful anti-tumor activity with a well-tolerated safety profile in patients with castration-resistant prostate cancer (CRPC) in phase I and II studies; however, the efficacy of currently approved CRPC therapies after treatment with galeterone is unknown. In this study, we evaluate prostate specific antigen (PSA) response of non-protocol therapies following galeterone in a subset of patients treated on the Androgen Receptor Modulation Optimized for Response (ARMOR) 2 study.

PATIENTS AND METHODS:

Patients who received any subsequent treatment were included. PSA response and treatment duration were summarized by line and type of subsequent therapy.

RESULTS:

Overall, 27 of 40 patients received ≥ 1 post-galeterone treatment, of whom 18 (67%) discontinued galeterone for progression, 14 (52%) received ≥ 2 treatments, and 6 (22%) received ≥ 3 treatments. PSA changed by a median of -36%, -35%, and +60% in patients receiving first-line, second-line, and third-line therapy, respectively. Overall, 18 (67%) received subsequent enzalutamide, 12 (44%) received docetaxel, 9 (33%) received abiraterone, and 5 (19%) received cabazitaxel. PSA changed by a median of -27%, -34%, -39%, and 17% for patients receiving subsequent enzalutamide, docetaxel, abiraterone, and cabazitaxel, respectively, at any line.

CONCLUSION:

We demonstrate that CRPC therapies exhibit differential anti-tumor activity following galeterone. In this small cohort, abiraterone demonstrates the highest PSA response post-galeterone, whereas enzalutamide and chemotherapy have more modest activity. Larger clinical studies are warranted to fully evaluate the efficacy and safety of second-generation hormonal agents and chemotherapy post-galeterone. Predictive biomarkers will be critical to optimizing patient selection for sequential therapies.

KEYWORDS:

Abiraterone; Androgen receptor degradation; CYP17 inhibition; Chemotherapy; Enzalutamide; Resistance

PMID:
27890446
DOI:
10.1016/j.clgc.2016.10.006
[Indexed for MEDLINE]

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