Disease Control Outcomes from Analysis of Pooled Individual Patient Data from Five Comparative Randomised Clinical Trials of Degarelix Versus Luteinising Hormone-releasing Hormone Agonists

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. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.