Degarelix 120mg 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

ObjectiveThe escalating incidence of prostate cancer poses a significant global public health challenge. Optimal utilization of resources is crucial for the effective deployment of funds among the diverse and emerging treatment options for managing prostate cancer. This systematic review aims to offer insights and serve as a reference for pharmacoeconomic studies related to the use of degarelix and luteinizing hormone-releasing hormone (LHRH) agonists in the treatment of prostate cancer.MethodsWe conducted a comprehensive search in databases including Embase, PubMed, the Cochrane Library, CNKI, Web of Science, Scopus, and the Tufts CEA Registry to identify cost-effectiveness studies on the use of degarelix and LHRH agonists in the treatment of prostate cancer, spanning from the inception of these databases up to December 30, 2025. Two independent reviewers sequentially examined titles, abstracts, and full-text articles, applying predefined inclusion and exclusion criteria to select studies for data extraction. Any disagreements were resolved through discussion until a consensus was reached. The quality of the included studies was evaluated using the Quality of Health Economic Studies and Consolidated Health Economic Evaluation Reporting Standards. Relevant data were then summarized and comparatively analyzed, focusing on aspects such as the model framework, model parameters, and uncertainty analysis.ResultsA total of 13 studies were ultimately incorporated, with an overall high quality but significant methodological variations among them. Five studies compared degarelix with leuprorelin, goserelin, or triptorelin; four compared triptorelin to goserelin or leuprorelin; one study evaluated leuprorelin acetate in a 6-month depot formulation vs. a 3-month depot; two compared leuprorelin to goserelin and triptorelin; and one study assessed radiotherapy vs. radiotherapy plus goserelin. Eight studies employed the Markov model, with time horizons spanning from 1 year to 30 years. The majority of the studies (n = 7) conducted cost-effectiveness analyses, and most were based in developed countries (n = 7). Degarelix was deemed cost-effective in the United States, United Kingdom, and China. Additionally, 6-month depot LHRH agonists were found to be more cost-effective than their monthly or 3-monthly counterparts.ConclusionFrom a societal perspective, the evidence suggests that degarelix may be a cost-effective option for patients with prostate cancer. All assessments of LHRH agonists are of high quality. Among the three LHRH agonists evaluated, the 6-month depot formulation of triptorelin may be a cost-effective option in certain settings. In clinical practice, the evaluation of a drug should comprehensively consider its efficacy, adverse effects, cost-effectiveness, and overall patient survival. The evidence is predominantly derived from high-income countries, and thus the conclusions may have limited generalizability to low- and middle-income country settings.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/recorddashboard, PROSPERO CRD420250653923.

Abstract licence: CC BY 4.0

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