Additional Analysis of the Secondary End Point of Biochemical Recurrence Rate in a Phase 3 Trial (CS21) Comparing Degarelix 80 mg Versus Leuprolide in Prostate Cancer Patients Segmented by Baseline Characteristics

作者：Tombal Bertrand^*; Miller Kurt; Boccon Gibod Laurent; Schroeder Fritz; Shore Neal; Crawford E David; Moul Judd; Jensen Jens Kristian; Olesen Tine Kold; Persson Bo Eric

来源：European Urology, 2010, 57(5): 836-842.

DOI：10.1016/j.eururo.2009.11.029

• Degarelix
• GnRH receptor antagonist
• GnRH receptor blocker
• Leuprolide
• Prostate cancer
• PSA

Background: Recent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients.
Objective: To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival.
Design, setting, and participants: Phase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo, and then 80 mg monthly (240/80 mg); degarelix at 240 mg for 1 mo, and then 160 mg monthly; and leuprolide at 7.5 mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer).
Measurements: PSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and >= 5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (<10, 10-20, >20-50, and >50 ng/ml) were analysed.
Results and limitations: Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p = 0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p = 0.04). The relatively low number of patients in each subgroup is a limitation of this study.
Conclusions: These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings.

• 出版日期2010-5