Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists.
BACKGROUND
Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate differences in outcomes.


OBJECTIVE
To assess differences in efficacy and safety outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists.


METHODS
Data were pooled from five prospective, phase 3 or 3b randomised trials (n=1925) of degarelix and leuprolide or goserelin in men requiring androgen deprivation therapy for the treatment of prostate cancer. Patients received either 3 mo (n=467) or 12 mo (n=1458) of treatment.


METHODS
Men were randomised to receive degarelix (n=1266), leuprolide (n=201), or goserelin (n=458).


METHODS
Unadjusted Kaplan-Meier analyses were supported by the Cox proportional hazards model, adjusted for disease-related baseline factors, to estimate hazard ratios (HRs) of efficacy and safety outcomes. The Fisher exact test compared crude incidences of adverse events.


CONCLUSIONS
Prostate-specific antigen (PSA) progression-free survival (PFS) was improved in the degarelix group (HR: 0.71; p=0.017). For patients with baseline PSA levels >20 ng/ml, the HR for PSA PFS was 0.74 (p=0.052). Overall survival (OS) was higher in the degarelix group (HR: 0.47; p=0.023). OS was particularly improved with degarelix in patients with baseline testosterone levels >2 ng/ml (HR: 0.36; p=0.006). 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.


CONCLUSIONS
These data indicate clinical benefits with 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.
Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. Electronic address: laurence.klotz@sunnybrook.ca.
Laurence
L
Klotz
Charité Universitätsmedizin Berlin, Berlin, Germany.
Kurt
K
Miller
University of Colorado, Denver, CO, USA.
E David
ED
Crawford
Carolina Urologic Research Center, Myrtle Beach, SC, USA.
Neal
N
Shore
Cliniques Universitaires Saint Luc/Université Catholique de Louvain, Brussels, Belgium.
Bertrand
B
Tombal
Ferring Pharmaceuticals, Copenhagen, Denmark.
Cathrina
C
Karup
Ferring Pharmaceuticals, Copenhagen, Denmark.
Anders
A
Malmberg
Ferring Pharmaceuticals, Saint-Prex, Switzerland.
Bo-Eric
BE
Persson
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors; D017273:Goserelin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D009842:Oligopeptides; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D017430:Prostate-Specific Antigen; D016729:Leuprolide
Androgen deprivation therapy; Degarelix; Goserelin; Leuprolide; Prostate cancer