What are the cardiac effects of Orgovyx (relugolix) and how are they managed in patients with pre-existing cardiovascular disease?

From the Guidelines

Orgovyx (relugolix) can cause QT prolongation and increase the risk of cardiovascular events in patients with pre-existing cardiovascular disease, and therefore, careful monitoring and management are essential to minimize these risks. In patients with a history of heart disease, stroke, or other cardiovascular conditions, careful monitoring is essential when initiating this medication. Before starting Orgovyx, patients should undergo baseline ECG assessment and evaluation of cardiovascular risk factors, as recommended by the ESMO consensus guidelines 1. During treatment, regular monitoring of QT intervals through ECG is recommended, particularly in the first few months of therapy. For patients with pre-existing cardiovascular disease, consider more frequent cardiac monitoring and address modifiable risk factors such as hypertension, diabetes, and hyperlipidemia. The standard dose of Orgovyx is 360 mg on the first day followed by 120 mg daily, but dose adjustments may be necessary based on cardiovascular response. If QT prolongation occurs or cardiovascular symptoms develop, temporary discontinuation or permanent cessation of Orgovyx may be required.

Some key considerations for managing cardiac effects of Orgovyx include:

• Baseline ECG assessment and evaluation of cardiovascular risk factors before starting treatment
• Regular monitoring of QT intervals through ECG, particularly in the first few months of therapy
• Addressing modifiable risk factors such as hypertension, diabetes, and hyperlipidemia
• Considering more frequent cardiac monitoring for patients with pre-existing cardiovascular disease
• Dose adjustments or temporary discontinuation of Orgovyx if QT prolongation or cardiovascular symptoms occur

The cardiac effects of Orgovyx occur because it is a GnRH antagonist, which reduces testosterone levels, impacting cardiovascular function through various mechanisms, including effects on lipid metabolism and vascular tone, as discussed in the context of cancer treatment and cardiovascular disease management 1. Management should involve a multidisciplinary approach with collaboration between oncologists and cardiologists to optimize patient safety while maintaining effective cancer treatment.

From the FDA Drug Label

The following clinically significant adverse reactions are described elsewhere in the labeling: QT/QTc Interval Prolongation [see Warnings and Precautions (5.1)]. Serious adverse reactions occurred in 12% of patients receiving ORGOVYX. Serious adverse reactions in ≥ 0.5% of patients included myocardial infarction (0.8%), acute kidney injury (0.6%), arrhythmia (0.6%), hemorrhage (0.6%), and urinary tract infection (0.5%). Fatal adverse reactions occurred in 0.8% of patients receiving ORGOVYX including metastatic lung cancer (0.3%), myocardial infarction (0.3%), and acute kidney injury (0.2%). Fatal and non-fatal myocardial infarction and stroke were reported in 2.7% of patients receiving ORGOVYX. Adverse reactions which resulted in permanent discontinuation of ORGOVYX in ≥ 0.3 % of patients included atrioventricular block (0.3%), cardiac failure (0.3%), hemorrhage (0.3%), increased transaminases (0.3%), abdominal pain (0.3%), and pneumonia (0.3%).

The cardiac effects of Orgovyx (relugolix) include:

• Myocardial infarction: reported in 0.8% of patients
• Arrhythmia: reported in 0.6% of patients
• Atrioventricular block: reported in 0.3% of patients
• Cardiac failure: reported in 0.3% of patients
• QT/QTc Interval Prolongation: a clinically significant adverse reaction described in the labeling In patients with pre-existing cardiovascular disease, the management of cardiac effects is not explicitly stated in the label. However, given the potential for cardiac adverse reactions, caution should be exercised when administering Orgovyx to these patients 2.

From the Research

Cardiac Effects of Orgovyx (Relugolix)

• The cardiac effects of Orgovyx (relugolix) have been studied in several clinical trials, including the phase III HERO trial 3, 4, 5, 6, 7.
• The results of these trials suggest that relugolix may be associated with a lower risk of major adverse cardiac events compared to leuprolide, a commonly used gonadotropin-releasing hormone (GnRH) agonist 3, 5, 6, 7.
• In the HERO trial, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group, representing a 54% lower risk with relugolix 7.
• The improved cardiac safety profile of relugolix may be due to its mechanism of action as a GnRH antagonist, which avoids the initial testosterone surge associated with GnRH agonists and may reduce the risk of cardiovascular events 5, 6.

Management of Cardiac Effects in Patients with Pre-Existing Cardiovascular Disease

• Patients with pre-existing cardiovascular disease may require closer monitoring and management while receiving relugolix therapy 4.
• The use of concomitant cardiovascular therapies, such as antihypertensives, antithrombotics, and lipid-modifying therapies, was common in the HERO trial and did not appear to affect the efficacy or safety of relugolix 4.
• However, the incidence and types of adverse events, including grade ≥3 and fatal adverse events, were similar between the relugolix and leuprolide groups, and some increases were observed in patients receiving concomitant cardiovascular therapies 4.
• Therefore, careful consideration and monitoring of cardiovascular risk factors and concomitant therapies are recommended when using relugolix in patients with pre-existing cardiovascular disease 4, 5, 6, 7.