According to findings from a long term study, men with prostate cancer (PCa) who are treated with degarelix (a newly approved gonadotropin-releasing hormone receptor (GnRH) blocker) have a lower risk of PSA failure or death compared with those treated with leuprolide.
The study included men with advanced PCa who previously had completed a pivotal one-year randomized phase 3 trial (CS21) that compared the two drugs. The trial demonstrated that degarelix suppressed PSA faster than leuprolide, a commonly used GnRH agonist, over the first 56 days of the trial. It also showed that degarelix was associated with a significantly lower risk of PSA failure or death during the one-year study period.
The new study, led by Neal Shore, MD, of Carolina Urologic Research Center in Myrtle Beach, S.C., (Dr. Shore was my interviewee on the recent Malecare Teleconference about Provenge) is an ongoing open-label extension trial that enrolled patients who completed CS21. At the fourth annual Genitourinary Cancers Symposium, Dr. Shore reported findings from 259 subjects, of whom 125 had received degarelix (a 240 mg starter dose followed by monthly 80 mg maintenance doses) and 134 had received leuprolide (7.5 mg per month) in CS21. In the extension trial, all patients received degarelix 240/80 mg.
The baseline characteristics between the patients who continued on degarelix and those who switched from leuprolide were generally comparable, according to the researchers.
After a median follow-up of 27.5 months, the PSA progression-free survival (PFS) hazard rates had decreased significantly from 0.20 events per year in the first year to 0.08 events per year following the switch in leuprolide patients, the study found. The corresponding hazard rates for the subjects who continued on degarelix were 0.11 and 0.14 events per year, respectively. Among patients with baseline PSA levels above 20 ng/mL, the hazard rates decreased significantly from 0.38 to 0.19 events per year among the patients who switched from leuprolide to degarelix and remained at 0.23 events per year among patients who continued on degarelix.
In addition, the time for 25% of patients with baseline PSA levels greater than 20 ng/mL to experience PSA failure or death was longer for degarelix recipients than for leuprolide-treated patients in the main trial (407 vs. 303 days) but the difference was not statistically significant. The difference was significant, however, when the investigators looked at data beyond one year (514 days for subjects who continued on degarelix compared with 303 days for those who switched from leuprolide).
“The long-term data support the durability of the significant progression-free survival benefit for degarelix treatment over monthly leuprolide seen during the first treatment year,” Dr. Shore told Renal & Urology News. Additionally, he noted, these data support the use of degarelix for first-line androgen deprivation therapy and demonstrate that the benefits of GnRH blockers compared with GnRH agonists extend beyond the rapid onset of action and flare suppression.
It would be very interesting to see this study carried out even further in time.
Joel T Nowak, M.A., M.S.W.
It would have been nice to know what happened to the testosterone levels of the men in the portion leuprolide arm where PSA advanced.