Degarelix versus LHRH agonists: Differential skeletal and urinary tract outcomes from an analysis of six comparative randomized clinical trials.

Abstract

68 Background: The use of ADT in men with prostate cancer is well established. GnRH antagonists have a mode of action distinct to that of LHRH agonists and comparative trials have shown differences in efficacy and safety between these agents. Adverse events (AE) from the musculoskeletal and renal and urinary systems have now been analysed. Methods: Results were pooled from 6 prospective, comparative randomised trials (n=2328). Most patients (pts) received 1 year of degarelix or LHRH agonist treatment (n=1686); the remaining men had 3–7 months’ treatment (n=642). AEs were analysed using Kaplan Meier plots and a log-rank test for homogeneity on relevant groups of MedDRA terms. Results: Treatment groups (degarelix, n=1491; LHRH agonist, n=837) were balanced for baseline characteristics such as age, testosterone, PSA and disease stage. In men with metastatic disease alkaline phosphatase (ALP) was reduced to a greater extent with degarelix (p=0.0373) throughout the year. Overall probability of fracture (<1% vs. 2%, p=0.0411) and incidence of joint related AEs (4% vs. 6%, p=0.0116) were significantly lower for degarelix-treated men. Incidence of muscle or bone pain was lower for degarelix (9% vs. 12%, p=0.0822). Incidence of urinary infections (UI) was reduced (5% vs. 8% with agonists) and time to first UI was significantly increased (p=0.0010) with degarelix. Overall probability of any renal or urinary tract AEs, including lower urinary tract symptoms (LUTS), was significantly lower in pts receiving degarelix (p<0.0001). Consistent with fewer skeletal and urinary tract AEs indicating better disease control, men with baseline PSA >50 ng/mL had significantly higher PSA PFS compared to agonist treated pts. OS during 1 year of treatment was significantly higher for degarelix pts (98.3% vs. 96.7%, p=0.0329). Conclusions: This analysis of 2,328 men shows degarelix-treated men had lower ALP, significantly fewer fractures, a lower incidence of urinary tract symptoms and higher overall survival than pts receiving an LHRH agonist over one year. Control of such disease symptoms is consistent with previous data on a significantly lower risk of PSA PFS during the first year of treatment.