Data Suggest Lower Risk of Cardiovascular Events or Deaths in Prostate Cancer Patients Treated with Degarelix Compared to LHRH Agonists

 Data presented today at the European Association of Urology (EAU) 2013 annual meeting in Milan, indicate that the gonadotropin releasing hormone (GnRH) antagonist degarelix (brand name: FIRMAGON®) may be associated with lower risk of a cardiovascular (CV) event or death compared to commonly prescribed luteinising hormone-releasing hormone (LHRH) agonists.1 These data are based on a pooled analysis of 2,328 men with prostate cancer from six prospective, randomised trials.  Analysis of the data also revealed that the men in the studies treated with FIRMAGON had significantly higher overall survival and improved disease control as evidenced by fewer fractures and a lower incidence of renal or urinary tract adverse events compared to men treated with LHRH agonists.2  
Risk of CV Events or Deaths  Concerns about the cardiovascular toxicity of LHRH agonists have been raised following the October 2010 warning by the US Food and Drug Administration (FDA) about an increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, and stroke). The FDA based its warning on the review of several published studies.3  
In the data presented at the EAU congress, results were pooled and retrospectively analysed from six prospective, comparative trials of 2,328 patients randomised to receive FIRMAGON (n=1,491) or an LHRH agonist (goserelin, n=458; leuprolide, n=379).  Both treatment groups were well balanced for baseline characteristics and history of CV disease (CVD).  Characteristics associated with CVD (e.g. statin medication, elevated blood pressure, diabetes, cholesterol >6.2mmol/L) were also similar between groups.  The CV event analysis was based on death from any cause or a serious CV event (life-threatening or requiring hospitalisation).  CV events were defined as arterial, embolic / thrombotic; haemorrhagic / ischemic cerebrovascular; myocardial infarction or other ischemic heart disease, whatever came first.  A time to event analysis for patients with baseline CVD demonstrated that the risk of a serious CV event or death was significantly lower for those men receiving FIRMAGON, compared to those receiving an LHRH agonist during the first year of treatment (p=0.0066 based on the log-rank test).  
 
“Our findings suggest that prostate cancer patients with a history of CVD treated with degarelix have a decreased incidence of a serious CV event or death during the first year of therapy compared to treatment with an LHRH agonist”, pointed out study investigator Professor Bertrand Tombal from the Cliniques Universitaires Saint Luc, Brussels. “These results are from a pooled analysis of prospective randomized trials. Although preliminary, healthcare professionals starting patients on androgen deprivation therapy should be aware of these important findings, including the fact that the observed difference in cardiovascular risk in patients with baseline CVD was approximately 50 percent lower for Firmagon vs. LHRH agonists.”  
Renal, Urinary Tract and Musculoskeletal Adverse Events (AEs)  The treatment groups were also analysed for differences in adverse events from the musculoskeletal, renal and urinary systems.  Findings from the pooled analysis showed that men treated with FIRMAGON had significantly fewer fractures, a lower incidence of any renal or urinary tract adverse events, and a higher overall survival compared to patients treated with LHRH Agonists.  
The overall probability of fracture and incidence of joint-related adverse events were significantly lower for FIRMAGON-treated men than those receiving an LHRH agonist, p=0.0234, and p=0.0116,4 respectively, based on the log-rank test. The incidence of muscle or bone pain was also lower for men treated with FIRMAGON (p=0.0822).2 The probability of any renal or urinary tract AEs was significantly lower in men receiving FIRMAGON (p<0 .0001="" 96.7="" agonist="" compared="" during="" firmagon="" for="" higher="" lhrh="" men="" nbsp="" of="" one="" p="" receiving="" significantly="" survival="" those="" to="" treated="" treatment="" verall="" vs.="" was="" with="" year="">“The improvement in disease control, higher overall survival, and reduction in musculoskeletal, renal and urinary system adverse events observed for prostate cancer patients treated with degarelix compared to LHRH agonist treatment, should be taken into consideration when considering treatment options for patients”, said Professor Kurt Miller, from Charité-Universitätsmedizin, Berlin.