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

作者：Klotz Laurence^*; Miller Kurt; Crawford E David; Shore Neal; Tombal Bertrand; Karup Cathrina; Malmberg Anders; Persson Bo Eric

来源：European Urology, 2014, 66(6): 1101-1108.

DOI：10.1016/j.eururo.2013.12.063

• Androgen deprivation therapy
• Degarelix
• Goserelin
• Leuprolide
• Prostate cancer

Background: Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate differences in outcomes. %26lt;br%26gt;Objective: To assess differences in efficacy and safety outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists. %26lt;br%26gt;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. %26lt;br%26gt;Intervention: Men were randomised to receive degarelix (n = 1266), leuprolide (n = 201), or goserelin (n = 458). %26lt;br%26gt;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. %26lt;br%26gt;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 %26gt;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 %26gt;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. %26lt;br%26gt;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.

• 出版日期2014-12