The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

Derek J Rosario,Bruce Turner,Heather Payne,James Green,Mike Kirby,Patrick Davey,Damien Greene

doi:10.1007/s00345-016-1818-2

Abstract

PurposeComparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC).MethodsThis article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions.ResultsIn randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture.ConclusionWhen making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease.

Highlights

Prostate cancer (PC) is the second most common cancer in men worldwide, with approximately 1.09 million men diagnosed in 2012, accounting for 15 % of all cancers in men [1]
In the UK, it is the most common cancer in men, with approximately 45,400 diagnoses and 10,600 deaths attributed to PC in 2012 [1]
Men with PC represent a high-risk population for cardiovascular disease, with many of the risk factors for PC being associated with high risk of CVD

Summary

Introduction

Prostate cancer (PC) is the second most common cancer in men worldwide, with approximately 1.09 million men diagnosed in 2012, accounting for 15 % of all cancers in men [1]. In men with pre-existing CVD, there was a 56 % lower risk of a cardiac event (absolute risk reduction 8.2 %) in the first year of initiating ADT with a GnRH antagonist than with a GnRH agonist (HR 0.44; 95 % CI 0.26–0.74; p = 0.002; number needed to treat = 12) [40] The magnitude of this risk reduction can be put into context by considering treatments intended to reduce risk in populations at high risk of CV events. Whereas this recommendation is based primarily on demonstration of improved QoL and reduction in fatigue [56], mechanistic evidence exists suggesting improvement in endothelial function from such an intervention, a possible impact on reducing CV risk [57]

Conclusions

Findings

Compliance with ethical standards