Prostate-specific antigen (PSA) progression-free survival (PFS): A comparison of degarelix versus leuprolide in patients with prostate cancer

12 Background: Comparative effectiveness of the gonadotropin-releasing hormone (GnRH) blocker, degarelix, vs the GnRH agonist, leuprolide, was evaluated during a 1-year phase III trial (CS21); data have been presented. We now report long-term data from an ongoing 5-year extension study (CS21A). Methods: In CS21, patients with prostate cancer (all stages) were randomized to degarelix (240 mg for 1 month, then monthly maintenance doses of 80 mg [n=207] or 160 mg [n=202]), or leuprolide 7.5 mg/month (n=201). Leuprolide patients could receive bicalutamide. Of the 504 patients who completed the 1-year trial, 384 chose to continue in an extension study; those on leuprolide were re-randomized to degarelix 240/80 mg or 240/160 mg. PSA PFS was defined as time to first PSA failure (two consecutive increases in PSA of 50% and ≥5 ng/mL above nadir) or death. Time for 25% of patients to experience PSA PFS (TTP25%) was analyzed using Weibull estimates. Results: Up to 1 year, the risk of PSA PFS was significantly lower with degarelix 240/80 mg vs leuprolide (p=0.05, log-rank). At 27.5 months' median follow-up, hazard rate of PSA PFS significantly decreased in leuprolide patients switched to degarelix compared with before the switch (0.20 vs 0.08; p=0.003). Similar improvements occurred in patients with baseline PSA >20 ng/mL. During the first year, TTP25% for patients with baseline PSA >20 ng/mL was numerically longer with degarelix vs leuprolide (407 vs 303 days; p=0.085); the difference was even greater when degarelix data were analyzed beyond 1 year (514 vs 303 days; p=0.01). Conclusions: Patients receiving degarelix had a significantly lower risk of PSA failure or death vs leuprolide during the first year of treatment. After switching to degarelix, patients who initially received leuprolide experienced a significantly lower rate of PSA failure or death. In patients with baseline PSA >20 ng/mL, TTP25% was significantly longer for degarelix patients. These data support the durability of the significant PSA PFS benefit of degarelix vs monthly leuprolide observed during the first year and the use of degarelix as first-line androgen deprivation therapy. [Table: see text]