title: Efficacy of Therapies After Galeterone in Patients With Castration-resistant Prostate Cancer.
abstract: 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 who received any subsequent treatment were included. PSA response and treatment duration were summarized by line and type of subsequent therapy.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address: Rmckay5@partners.org.
authors.forename: Rana R
authors.initials: RR
authors.lastname: McKay
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Fiorillo
authors.affiliation: Clinical Operations and Program Management, Tokai Pharmaceuticals, Cambridge, MA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roberts
authors.affiliation: Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Heath
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Bubley
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Robert Bruce
authors.initials: RB
authors.lastname: Montgomery
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
mesh_terms: D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000494:pharmacology; D000736:Androstenes / Q000008:administration & dosage* / Q000494:pharmacology; D001549:Benzamides; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D004358:Drug Therapy; D006801:Humans; D007610:Kallikreins / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000187:drug effects; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000736:Androstenes; D001549:Benzamides; D001562:Benzimidazoles; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; C089740:abiraterone; C500627:3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene
keywords: Abiraterone; Androgen receptor degradation; CYP17 inhibition; Chemotherapy; Enzalutamide; Resistance