Efficacy of therapies after galeterone in patients with castration-resistant prostate cancer

• Published in: Clinical genitourinary cancer 2017-08, Vol.15 (4), p.463-471
• Main Authors: McKay, Rana R., MD, Werner, Lillian, MS, Fiorillo, Matthew, BA, Roberts, Jennifer, BA, Heath, Elisabeth, MD, Bubley, Glenn J., MD, Montgomery, Bruce, MD, Taplin, Mary-Ellen, MD
• Format: Article
• Language: English
• Subjects: Abiraterone; Aged; Androgen receptor degradation; Androstadienes - administration & dosage; Androstadienes - pharmacology; Androstenes - administration & dosage; Androstenes - pharmacology; Benzimidazoles - administration & dosage; Benzimidazoles - pharmacology; Chemotherapy; CYP17 inhibition; Drug Therapy; Enzalutamide; Hematology, Oncology and Palliative Medicine; 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; Resistance; Survival Analysis; Treatment Outcome; Urology
• ISSN: 1558-7673; 1938-0682
• DOI: 10.1016/j.clgc.2016.10.006

Background Galeterone is a multi-targeted agent with activity as a CYP17 inhibitor, androgen receptor (AR) antagonist, and also causes AR degradation. It has shown meaningful anti-tumor activity with a well-tolerated safety profile in patients with castration-resistant prostate cancer (CRPC) in phase 1/2 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 ARMOR2 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, 27/40 patients received ≥1 post-galeterone treatment of whom 18(67%) discontinued galeterone for progression, 14(52%) received ≥2, and 6(22%) received ≥3. 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.