VAIL, CO USA (UroToday.com) - Background: Short-term antiandrogen (AA) flare protection is used to counter the clinical effects of the testosterone surge associated with luteinizing hormone-releasing hormone (LHRH) agonist therapy.
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Degarelix, a gonadotrophin-releasing hormone antagonist, does not cause testosterone surge. Individual patient data from two phase III trials have been pooled to compare the 1 year efficacy of degarelix monotherapy vs. combined LHRH agonist + AA flare protection.
Methods: Data were pooled from two randomized, one-year studies; CS21 compared monthly degarelix with leuprolide and CS35 compared 3-month formulations of degarelix and goserelin. AA was administered in the LHRH agonist groups at the investigator’s discretion. Analyses were performed by the Kaplan-Meier method and log-rank test (probability of PSA progression-free survival [PFS]), Cox regression (adjusted hazard ratios [HR] for PSA PFS failure) and repeated measures ANCOVA (serum alkaline phosphatase [S-ALP]).
Results: In total, 974 patients received degarelix and 69 patients a LHRH agonist + AA. The LHRH agonist + AA group contained a higher proportion of patients with Gleason score 7-10, metastatic disease, or baseline PSA >50 ng/mL compared with the degarelix group. Cox regression was used to account for these baseline differences. Testosterone and PSA surges remained at Day 3, with increases in mean testosterone and PSA of >50% and >20%, respectively, with LHRH agonist + AA flare protection. With degarelix treatment, mean testosterone was reduced by >80% and PSA was unchanged at Day 3. PSA PFS failure rate (adjusted for baseline PSA, prostate cancer stage and Gleason score) was significantly lower for all patients with degarelix than with LHRH agonist + AA flare protection (HR=0.490, p=0.0028). PSA PFS failure rate was also lower with degarelix compared with LHRH agonists + AA for patients with baseline PSA >20 ng/mL (HR=0.500, p=0.0073) or metastatic disease (HR=0.52, p=0.0198). Overall, 5 patients (7.2%) died in the LHRH agonist + AA group and 18 patients (1.9%) in the degarelix group. The overall mortality rate (adjusted for age, baseline PSA, prostate cancer stage and Gleason score) was significantly lower with degarelix than with LHRH agonist + AA (HR=0.366, p=0.0486). S-ALP levels in metastatic patients and those with baseline PSA >50 ng/mL during the year of treatment were significantly lower with degarelix (p=0.0025 and 0.0005, respectively). S-ALP fell below baseline by ≤2 months with degarelix and ≤7 months with LHRH agonist + AA.
Conclusion: This pooled analysis indicates LHRH agonist + AA therapy flare protection may not achieve similar disease control as degarelix monotherapy during the first year of therapy in patients at high risk of symptomatic disease progression.
Presented by E. David Crawford, Jan-Erik Damber, Anders Malmberg, Bo-Eric Persson, Laurence Klotz, and Peter Iversen at the 24th International Prostate Cancer Update - February 19 - 22, 2014 - Cascade Conference Center - Vail, Colorado USA
24th Int'l Prostate Cancer Update, luteinizing hormone-releasing hormone (LHRH), degarelix, anti-androgen (AA) flare