Degarelix 80mg powder and solvent for solution for injection vials

Background and objectiveGonadotropin-releasing hormone (GnRH) antagonists and agonists are cornerstone treatments in prostate cancer. However, evidence regarding the comparative cardiovascular safety of these drugs from clinical trials is inconclusive. The objective of this study was to systematically assess the risk of adverse cardiovascular events of GnRH antagonists compared with GnRH agonists across real-world evidence studies.MethodsWe conducted a systematic search of PubMed, Embase, Cochrane Library, Scopus, and Web of Science (2008-2023). We included real-world evidence studies comparing the risk of cardiovascular outcomes of GnRH antagonists with those of GnRH agonists among patients with prostate cancer. We conducted a meta-analysis of effect estimates across studies at a low or moderate risk of bias, assessed via the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool, using random-effect models.Key findings and limitationsAmong ten included studies, four were classified as having a moderate and six as having a serious risk of bias. Across three studies at a moderate risk of bias in the primary analysis, degarelix was associated with an increased risk (pooled relative risk [RR]: 1.31, 95% confidence interval [CI]: 1.14-1.51) of major adverse cardiovascular events (MACEs). An augmented risk was observed in two studies among patients with a history of cardiovascular disease (pooled RR: 1.31, 95% CI: 1.11-1.56) compared with one study among patients without a history of cardiovascular disease (RR: 1.15, 95% CI: 0.83-1.59).Conclusions and clinical implicationsReal-world evidence studies indicate that degarelix, compared with GnRH agonists, is associated with a modest increased risk of MACEs, particularly among patients with a history of cardiovascular disease. However, residual confounding due to the treatment of high-risk patients with degarelix may account for these findings. Additional large studies with detailed data on tumor characteristics and cardiovascular risk factors are needed to confirm these findings.Patient summaryIn this systematic evaluation of evidence among patients diagnosed with prostate cancer in routine care, degarelix was associated with higher cardiovascular adverse outcomes than gonadotropin-releasing hormone agonists.

Abstract licence: CC BY-NC-ND

Relugolix is a novel orally administered gonadotropin-releasing hormone (GnRH) antagonist approved for androgen deprivation therapy (ADT) in advanced prostate cancer. Its oral formulation, rapid onset of action, and potentially improved cardiovascular safety profile distinguish it from traditional injectable GnRH antagonists. This review evaluates current primary research on the clinical effectiveness and safety of Relugolix compared to established ADT agents. A structured literature search was conducted using PubMed, targeting primary research articles that assessed the efficacy and safety of oral Relugolix. Inclusion criteria comprised original studies with clinical endpoints such as testosterone suppression, prostate-specific antigen (PSA) response, and castration resistance-free survival (CRFS). Exclusion criteria included reviews, meta-analyses, and studies not investigating Relugolix. Searches were completed by two independent reviewers compared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Nine primary studies met the inclusion criteria, including randomized controlled trials (RCTs), subgroup analyses, pharmacokinetic modelling, and observational studies. In the HERO trial, Relugolix achieved castration-level testosterone (<50 ng/dL) in 96.7% of patients, outperforming Leuprolide (88.3%) in both speed (median = 4 days vs. 29 days) and magnitude of suppression. Subgroup analyses demonstrated consistent efficacy across patients receiving concomitant therapies with a lower incidence of major cardiovascular events in the Relugolix group. Additional studies confirmed its effectiveness when combined with radiotherapy in comparison with Degarelix. Pharmacokinetic modelling supported rapid and sustained testosterone suppression even during short treatment interruptions. Relugolix is an effective and well-tolerated oral GnRH antagonist for patients with advanced prostate cancer. It offers rapid testosterone suppression, high rates of CRFS, and a potentially favorable cardiovascular safety profile compared to injectable ADT agents. These advantages, along with oral administration, support its use as a viable alternative in clinical practice. Further long-term studies are warranted to confirm sustained outcomes and optimize treatment regimes.

Abstract licence: CC BY

BackgroundAndrogen deprivation therapy (ADT) is a cornerstone treatment for advanced prostate cancer. While effective, traditional injectable luteinizing hormone-releasing hormone (LHRH) agonists are associated with an initial testosterone flare and potential cardiovascular risks. Relugolix is a novel, oral gonadotropin-releasing hormone (GnRH) antagonist developed to provide rapid suppression without a testosterone flare. This review synthesizes the latest evidence on the efficacy, safety, and clinical utility of relugolix.MethodsThis non-systematic review was conducted via a search of PubMed and MEDLINE databases up to July 2025 using the terms "relugolix" AND "ADT" OR "Androgen Deprivation Therapy" AND "Prostate Cancer." Only original studies in English were included.ResultsThe phase III HERO trial established the superiority of relugolix over leuprolide, demonstrating higher rates of sustained castration (96.7% vs 88.8%) and a significantly faster onset of action. Relugolix also showed a 54% reduction in major cardiovascular adverse events. Furthermore, it exhibited equivalent efficacy to injectable degarelix when combined with radiotherapy, but with more robust testosterone recovery after treatment cessation (52% vs 16%). Real-world data indicates high patient adherence to the oral regimen, and a cost-effectiveness analysis suggests it is a cost-effective option despite a higher drug cost.ConclusionsRelugolix represents a significant advancement in ADT, offering a potent, oral alternative with a rapid onset of action, a superior cardiovascular safety profile, and improved testosterone recovery. It provides clinicians with a valuable option for treating advanced prostate cancer, particularly in patients with cardiovascular comorbidities.

Abstract licence: CC BY-NC