Laurence Klotz1, Kurt Miller2, E David Crawford3, Neal Shore4, Bertrand Tombal5, Cathrina Karup6, Anders Malmberg6, Bo-Eric Persson7. 1. Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. Electronic address: laurence.klotz@sunnybrook.ca. 2. Charité Universitätsmedizin Berlin, Berlin, Germany. 3. University of Colorado, Denver, CO, USA. 4. Carolina Urologic Research Center, Myrtle Beach, SC, USA. 5. Cliniques Universitaires Saint Luc/Université Catholique de Louvain, Brussels, Belgium. 6. Ferring Pharmaceuticals, Copenhagen, Denmark. 7. Ferring Pharmaceuticals, Saint-Prex, Switzerland.
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.
RCT Entities:
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.