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

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

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.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Androstadienes / administration & dosage*
  • Androstadienes / pharmacology
  • Androstenes / administration & dosage*
  • Androstenes / pharmacology
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / pharmacology
  • Drug Therapy
  • Humans
  • Kallikreins / blood*
  • Kallikreins / drug effects
  • Male
  • Middle Aged
  • Phenylthiohydantoin / administration & dosage
  • Phenylthiohydantoin / analogs & derivatives
  • Phenylthiohydantoin / pharmacology
  • Prostate-Specific Antigen / blood*
  • Prostate-Specific Antigen / drug effects
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Androstadienes
  • Androstenes
  • Benzimidazoles
  • Phenylthiohydantoin
  • enzalutamide
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen
  • abiraterone
  • 3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene