From the Guidelines
Relugolix is used in men with advanced prostate cancer as an oral GnRH antagonist to rapidly suppress testosterone levels, helping to slow the growth of prostate cancer cells. The medication is typically administered with a loading dose of 360 mg on the first day, followed by a daily dose of 120 mg. This approach allows for immediate hormone suppression without the initial testosterone surge seen with traditional GnRH agonists 1. Key benefits of relugolix include its oral formulation, which offers an alternative to injectable hormone therapies, and the potential for quicker recovery of testosterone levels if treatment is discontinued. Common side effects associated with relugolix include hot flashes, fatigue, constipation, diarrhea, and musculoskeletal pain. It is essential for men taking relugolix to be aware of the potential cardiovascular risks, particularly if they have pre-existing cardiovascular disease. Regular monitoring of PSA levels and testosterone is crucial while on treatment to assess the effectiveness of relugolix and adjust the treatment plan as needed. In the context of prostate cancer management, relugolix provides a valuable option for suppressing testosterone levels, which is a critical component of treating advanced prostate cancer, as highlighted in recent guidelines considering treatment intensification and the use of novel systemic agents 1.
From the FDA Drug Label
Relugolix is a nonpeptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, thereby, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and consequently testosterone. Pituitary and Gonadal Hormones Relugolix reduced LH, FSH, and testosterone concentrations after oral administration of the recommended loading dose of 360 mg and a 120 mg dose once daily Out of 622 patients, 56% had testosterone concentrations at castrate levels (< 50 ng/dL) by the first sampling timepoint at Day 4, and 97% maintained castrate levels of testosterone through 48 weeks
The use of Relugolix (relugolix) in men is to reduce testosterone concentrations by competitively binding to pituitary GnRH receptors, thereby reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This is achieved through oral administration of a recommended loading dose of 360 mg and a 120 mg dose once daily, resulting in castrate levels of testosterone in a significant percentage of patients 2.
- Key points:
- Reduces LH, FSH, and testosterone concentrations
- Achieves castrate levels of testosterone in most patients
- Administered orally with a loading dose and daily maintenance dose
- Mechanism of action: GnRH receptor antagonist
- Indication: Not explicitly stated in the provided label, but implied to be for conditions requiring testosterone reduction, such as prostate cancer 2
From the Research
Use of Relugolix in Men
- Relugolix is an orally active nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist used for the treatment of advanced prostate cancer 3.
- It provides rapid testosterone suppression and is indicated in the USA for the treatment of advanced prostate cancer and in the EU for advanced hormone-sensitive prostate cancer 3.
- In the pivotal phase III HERO trial, relugolix led to a sustained castration rate over 48 weeks of treatment of >90%, which was non-inferior to that provided by intramuscular leuprolide depot every 3 months 3.
- Relugolix was generally well tolerated, with an adverse event profile consistent with testosterone suppression, and may be associated with a lower risk of major adverse cardiac events compared with leuprolide 3, 4, 5.
- The HERO study showed that more men taking relugolix (97%) achieved sustained castration through 48 weeks than men receiving leuprolide (89%) 6.
- Relugolix had similar efficacy for men with or without castration resistance-free survival progression events 7.
- Relugolix offers a new treatment option for men with advanced prostate cancer, with the potential benefits of oral administration and improved cardiac safety 4, 5.
Benefits of Relugolix
- Rapid testosterone suppression without initial surge in testosterone upon treatment initiation 3, 4.
- Sustained castration rates over 48 weeks of treatment 3, 6.
- Potential for improved cardiac safety compared with leuprolide 3, 4, 5.
- Oral administration, which may improve patient compliance and quality of life 4, 5.
- Faster post-treatment recovery of testosterone levels compared with leuprolide 4.