Degarelex (Firmagon) (approved by the FDA in December of 2008) is a hormonal therapy drug used to treat advanced prostate cancer that has become metastatic and castrate resistant (mCRPC). Degarelix is a GnRH receptor that binds to the pituitary GnRH receptors, reducing the release of gonadotropins leading to a quick and profound onset that blocks the production of testosterone. It is known as a gonadotropin-releasing hormone antagonist

Prior to the development and approval of Degarelix the only FDA approved category of drugs that also reduces the production of testosterone are the GnRH agonists (Lupron, Trelstar, Zoladex, etc.), but they cause an initial stimulation of the hypothalamic-pituitary gonadal axis causing an initial surge in testosterone. This surge can cause fast and significant progression of the prostate cancer.

Our understanding the real differences in the outcomes of these drugs is important. Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists confirm there are differences in outcomes.

Data were pooled from five prospective, phase 3 or 3b randomized trials (n=1925) of degarelix and leuprolide or goserelin in men requiring androgen deprivation therapy for the treatment of prostate cancer. Men received either 3 months (n=467) or 12 months (n=1458) of treatment. The men were randomized to receive degarelix (n=1266), leuprolide (n=201), or goserelin (n=458).

The researchers found that Prostate-specific antigen (PSA) and progression-free survival (PFS) was improved in the degarelix group. For men with baseline PSA levels greater than 20 ng/ml overall survival (OS) was higher in the degarelix group. OS was particularly improved with degarelix in men with baseline testosterone levels greater than 2 ng/ml. In terms of disease-related adverse events, there were, overall, fewer joint-related signs and symptoms, musculoskeletal events, and urinary tract events in the degarelix group.

These data indicate superior clinical benefits with men who use degarelix, including a significant improvement in PSA PFS and OS, as well as reduced incidence of joint, musculoskeletal, and urinary tract adverse events, compared with LHRH agonists.

Eur Urol. 2014 Jan 9. pii: S0302-2838(13)01491-7.
doi: 10.1016/j.eururo.2013.12.063: Klotz L, Miller K, Crawford ED, Shore N, Tombal B, Karup C, Malmberg A, Persson BE

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