Based on six recent retrospective analyses comparing the gonadotropin-releasing hormone (GnRH) antagonist degarelix against the traditional luteinizing hormone-releasing hormone (LHRH) agonists (i.e. Zoladex, Lupron etc.) men with advanced prostate cancer experienced improved disease control, fewer instances of urinary infections, and a lower risk of cardiovascular events.

The six analyses compared data from randomized trials that included a sample of 2328 men who took either degarelix or an LHRH agonist—leuprolide acetate or goserelin—for three months to a year. The various findings of the six studies was presented in separate abstracts during the most recent annual meeting of the American Urological Association (AUA.

The two different groups of men were balanced for items such as age, disease stage, and levels of testosterone and prostate-specific antigen (PSA), said Neal D. Shore, MD, medical director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina, who presented findings that compared disease control-related outcomes.1

Dr. Shore also reported that muscle or bone pain was more likely to occur among those men who took the LHRH, with 12% of those men reporting such symptoms, compared with 9% of those on the degarelix arm (P = .0822). Additionally, the degarelix men faced a <1% probability of bone fracture versus a 2% probability for LHRH patients (P = .0411), and a 4% rate of joint-related adverse events (AEs) versus a 6% rate for LHRH patients (P = .0116).

Among men with metastatic disease who were treated for a year, those who took degarelix experienced a greater reduction in alkaline phosphatase (ALP) (P = .0373).  This might be important because a 2006 study found that, when controlling for other prognostic variables among men with hormone-refractory metastatic prostate cancer, higher levels of serum bone-specific ALP were associated with shorter survival.2

The pooled analysis comparing the GnRH antagonist to LHRH agonists also demonstrated that “there was a significantly lower overall probability of urinary tract AEs (P <.0001) and a significantly longer time to first urinary infection (P = .0010) in men treated with degarelix,” according to the abstract. Five percent of degarelix patients experienced urinary infections, as compared with 8% of those taking LHRH agonists.

Finally, in men with a baseline PSA >50 ng/mL, those treated with degarelix demonstrated significantly better PSA progression-free survival at one year versus men treated with LHRH agonists (66% vs 54.7%; P = .0245). Across all participating patients, overall survival in the first year of treatment was significantly higher for those taking degarelix (98.3% vs 96.7%; P = .0329).

Data on those outcomes, presented during the AUA meeting by Albertsen, et al,3 showed that treatment with degarelix instead of an LHRH agonist decreased the risk of subsequent serious cardiovascular events by greater than 50% for men with a history of cardiovascular disease.  However, in men with no prior cardiovascular disease, there was no difference between groups.

The combination of these studies “took men eligible for hormone therapy and randomized them to a loading dose and a maintenance dose of degarelix versus monthly leuprolide acetate, mainly Lupron, and basically, at the end of one year, both of those drugs were equivalent in maintaining castration and suppression way above 95%.  Additionally, with degarelix there was no flare in testosterone or PSA, eliminating the need to use Casodex as a part of the ADT.

  1. Shore N, Miller K, Tombal B. Analysis of disease control-related outcomes from six comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists. Presented at: American Urological Association Annual Meeting: May 4-8, 2013; San Diego, CA. Abstract 716.
  2. Cook RJ, Coleman R, Brown J, et al. Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res. 2006;12(11 Pt 1):3361-3367.
  3. Albertsen P, Tombal B, Wiegel T, et al. Androgen deprivation therapy by a gonadotropin releasing hormone antagonist, degarelix, lowers the risk of cardiovascular events or death when compared to luteinising hormone-releasing agonists. Presented at: American Urological Association Annual Meeting; May 4-8, 2013; San Diego, CA. Abstract 781.

Joel T. Nowak, M.A., M.S.W.