582 CARDIOVASCULAR SAFETY OF DEGARELIX: RESULTS FROM A 12-MONTH, COMPARATIVE, RANDOMIZED, OPEN-LABEL, PARALLEL-GROUP PHASE III TRIAL IN PROSTATE CANCER PATIENTS

Article Outline

• INTRODUCTION AND OBJECTIVES
• METHODS
• RESULTS
• CONCLUSIONS
• Copyright

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INTRODUCTION AND OBJECTIVES 

In men with prostate cancer, gonadotropin-releasing hormone (GnRH) agonists are associated with greater risk for myocardial infarction and death. Less is known about the cardiovascular (CV) safety profile of GnRH antagonists. We aimed to evaluate the CV related safety of degarelix (a new antagonist) compared with leuprolide (agonist).

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METHODS 

Patients had completed a 1-year randomised, controlled trial of degarelix 240/80 mg (n=202) or 240/160 mg (n=207) vs leuprolide acetate 7.5 mg (n=201). Patients were excluded from the study if they had marked baseline prolongation of QTc interval >450 ms or a history of additional risk factors for torsades de pointes ventricular arrhythmias. CV adverse events (AEs) and changes in the QT interval were analysed as well as baseline risk factors for CV events: concurrent cardiovascular disease, diabetes, hypertension, concomitant medications for diabetes and cardiovascular disease. Patients (n=46) with a baseline QRS >120 ms were excluded from the analysis of QT/QTc changes.

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RESULTS 

Nine percent of degarelix and 13% of leuprolide treated patients experienced AEs classed as cardiac disorders (p=0.089). The most frequently reported AEs in this class occurred with similar frequency in the degarelix and leuprolide groups: supraventricular arrhythmias (2 vs 4%), acute coronary syndromes (<1 vs 3%), coronary artery disease (2 vs 2%), cardiomyopathy (2 vs 2%) and atrioventricular conduction disturbances (<1 vs 1%). Fatal CV-related events occurred in 1% of degarelix and 2% of leuprolide treated patients. The time to first cardiac or vascular AE was analysed using Cox regression. There were no statistically significant differences by treatment arm, medical history of cardiac or vascular disorders, diastolic and systolic blood pressure, pre-trial medication for CV disorders or diabetes or cholesterol. There were no significant differences using the high level group term ‘cardiac arrhythmias'. Mean change in QTc to Cmax of treatment or until 1 year was not significantly different between treatment groups. A post-baseline QTc of '450 ms was noted for 17% of degarelix and 15% of leuprolide treated patients. Post-baseline QTc values ≥500 ms occurred in <1% patients treated with degarelix and 1% patients treated with leuprolide.

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CONCLUSIONS 

Rates of CV adverse events were low and similar for men who received degarelix and those who received leuprolide acetate in this 1-year study. Deaths related to CV-events did not appear to be due to prolongation of the QT interval.