title: Impact of baseline corticosteroids on survival and steroid androgens in metastatic castration-resistant prostate cancer: exploratory analysis from COU-AA-301.
abstract: BACKGROUND
  Corticosteroids have been used to mitigate mineralocorticoid-related effects and restore sensitivity to abiraterone acetate. Corticosteroids may also mediate glucocorticoid receptor or mutated androgen receptor activation and adversely influence outcome.
  
  
  OBJECTIVE
  This post hoc exploratory analysis investigated whether baseline corticosteroids were an independent prognostic factor and its level of contribution in the presence of other prognostic factors for overall survival (OS) in study COU-AA-301.
  
  
  METHODS
  COU-AA-301 was a randomised study of abiraterone plus prednisone versus prednisone in metastatic castration-resistant prostate cancer patients after docetaxel.
  
  
  METHODS
  Patients were randomised 2:1 to abiraterone 1000 mg plus prednisone 5mg by mouth twice daily versus prednisone.
  
  
  METHODS
  Association of OS with baseline corticosteroids was determined by univariate and multivariate Cox models.
  
  
  CONCLUSIONS
  At study entry, 33% of patients received corticosteroids, had worse disease characteristics (p<0.05 except liver metastases), and were more likely to have testosterone levels below the median (odds ratio: 2.92; chi-square p<0.0001). Associations between prostate-specific antigen response as well as circulating tumour cell decline and higher baseline androgen levels were demonstrated. Patients taking baseline corticosteroids had inferior OS in univariate analysis (hazard ratio: 1.48; p<0.0001); however, in multivariate stepwise selection modelling, baseline corticosteroids did not add substantially to the model. This analysis is limited as a retrospective analysis and restricted to patients after docetaxel.
  
  
  CONCLUSIONS
  In the COU-AA-301 study, baseline corticosteroids were associated with adverse prognostic features, inferior OS, and lower baseline androgen levels but did not add substantial information to the final prognostic model. Thus in these data from study COU-AA-301, concurrent baseline corticosteroids did not have an independent impact on OS.
  
  
  RESULTS
  Baseline corticosteroids did not adversely affect abiraterone clinical benefit in metastatic castration-resistant prostate cancer. Their use was associated with patients having worse disease characteristics.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: rbmontgo@uw.edu.
authors.forename: Bruce
authors.initials: B
authors.lastname: Montgomery
authors.affiliation: Janssen Research and Development, Los Angeles, CA, USA.
authors.forename: Thian
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: Janssen Research and Development, Menlo Park, CA, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.affiliation: Janssen Research and Development, Raritan, NJ, USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Janssen Research and Development, Los Angeles, CA, USA.
authors.forename: NamPhuong
authors.initials: N
authors.lastname: Tran
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Efstathiou
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Sutton, UK.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000305:Adrenal Cortex Hormones / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D000736:Androstenes; D000970:Antineoplastic Agents; D015415:Biomarkers; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; C089740:abiraterone; D011241:Prednisone
keywords: Abiraterone; Corticosteroids; Prostate cancer; Survival; Testosterone