Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists

Eur Urol. 2014 Dec;66(6):1101-8. doi: 10.1016/j.eururo.2013.12.063. Epub 2014 Jan 9.

Abstract

Background: Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate differences in outcomes.

Objective: To assess differences in efficacy and safety outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists.

Design, setting, and participants: Data were pooled from five prospective, phase 3 or 3b randomised trials (n=1925) of degarelix and leuprolide or goserelin in men requiring androgen deprivation therapy for the treatment of prostate cancer. Patients received either 3 mo (n=467) or 12 mo (n=1458) of treatment.

Intervention: Men were randomised to receive degarelix (n=1266), leuprolide (n=201), or goserelin (n=458).

Outcome measurements and statistical analysis: Unadjusted Kaplan-Meier analyses were supported by the Cox proportional hazards model, adjusted for disease-related baseline factors, to estimate hazard ratios (HRs) of efficacy and safety outcomes. The Fisher exact test compared crude incidences of adverse events.

Results and limitations: Prostate-specific antigen (PSA) progression-free survival (PFS) was improved in the degarelix group (HR: 0.71; p=0.017). For patients with baseline PSA levels >20 ng/ml, the HR for PSA PFS was 0.74 (p=0.052). Overall survival (OS) was higher in the degarelix group (HR: 0.47; p=0.023). OS was particularly improved with degarelix in patients with baseline testosterone levels >2 ng/ml (HR: 0.36; p=0.006). In terms of disease-related adverse events, there were, overall, fewer joint-related signs and symptoms, musculoskeletal events, and urinary tract events in the degarelix group.

Conclusions: These data indicate clinical benefits with degarelix, including a significant improvement in PSA PFS and OS, as well as reduced incidence of joint, musculoskeletal, and urinary tract adverse events, compared with LHRH agonists.

Keywords: Androgen deprivation therapy; Degarelix; Goserelin; Leuprolide; Prostate cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Disease-Free Survival
  • Gonadotropin-Releasing Hormone / agonists*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Goserelin / adverse effects
  • Goserelin / therapeutic use*
  • Humans
  • Leuprolide / adverse effects
  • Leuprolide / therapeutic use*
  • Male
  • Middle Aged
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Randomized Controlled Trials as Topic
  • Survival Rate
  • Testosterone / blood
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Oligopeptides
  • acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide
  • Goserelin
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Prostate-Specific Antigen
  • Leuprolide