title: Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus anti-androgen flare protection in advanced prostate cancer: an analysis of two randomized controlled trials.
abstract: OBJECTIVE
  The objective of this study was to assess differences in efficacy outcomes between luteinizing hormone-releasing hormone (LHRH) agonist plus antiandrogen (AA) flare protection and monotherapy with the gonadotrophin-releasing hormone antagonist degarelix in patients with prostate cancer.
  
  
  METHODS
  Data from 1455 patients were pooled from two prospective, phase III randomized 1-year clinical trials of degarelix versus LHRH agonist with or without AA. The AA bicalutamide was administered at the investigator's discretion. Adjusted hazard ratios (HRs) were calculated using a Cox proportional hazards regression model and a conditional logistic regression model was used for a case-control analysis of odds ratios (ORs).
  
  
  RESULTS
  Patients received degarelix monotherapy (n = 972) or LHRH agonist (n = 483) of whom 57 also received AA. Overall, prostate-specific antigen progression-free survival (PSA PFS) was improved with degarelix versus LHRH agonist + AA (Cox proportional hazards regression model-adjusted HR for PSA PFS failure was 0.56 [95% confidence interval (CI) 0.33-0.97, p = 0.038]). To compensate for a higher proportion of patients with metastases, Gleason score 7-10, and PSA >20 ng/ml in the LHRH agonist + AA group, a case-control analysis using a conditional logistic regression model was utilized. This resulted in an OR for PSA PFS of 0.42 (95% CI 0.20-0.89; p = 0.023) in the overall population, and 0.35 (95% CI 0.13-0.96; p = 0.042) in patients with PSA >50 ng/ml at baseline, when treated with degarelix versus LHRH agonists + AA. There were a small number of deaths, 1.9% with degarelix and 7% with LHRH agonists + AA (case-control analysis OR = 0.37; p = 0.085).
  
  
  CONCLUSIONS
  Degarelix monotherapy produced a more favorable effect on PSA PFS outcomes than a LHRH agonist + AA flare protection therapy in patients with prostate cancer when a case-control analysis was used to compensate for differences between treatment groups.
authors.affiliation: Copenhagen Prostate Cancer Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Institute of Clinical Sciences, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Damber
authors.affiliation: Ferring Pharmaceuticals, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Malmberg
authors.affiliation: Läkarhuset/Urologi, Läkarhuset and Uppsala University, St Persgatan 17, 5, SE 753 20 Uppsala, Sweden.
authors.forename: Bo-Eric
authors.initials: BE
authors.lastname: Persson
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
keywords: anti-androgen; degarelix; luteinizing hormone-releasing hormone agonist; prostate cancer; testosterone flare