Relugolix for treating hormone-sensitive prostate cancer

Relugolix is an orally active non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist that provides rapid testosterone suppression (1):

• indicated in the USA for the treatment of advanced prostate cancer and in the EU for advanced hormone-sensitive prostate cancer
• androgen deprivation therapy (ADT), a key component of prostate cancer treatment, reduces testosterone production to slow disease progression
  • most commonly, ADT involves the use of a gonadotropin-releasing hormone (GnRH) agonist [also known as luteinizing-releasing hormone (LHRH) agonists] (e.g., goserelin, histrelin, leuprolide, triptorelin), either alone or in combination with external beam radiation therapy or other systemic therapeutic agents
    • initiation of GnRH agonist therapy is associated with an initial acute (1–3-week) surge in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone
• whereas some ADT agents (i.e. GnRH agonists) produce an initial surge in testosterone levels (with the potential to cause a flare in disease symptoms), GnRH receptor antagonists, of which relugolix is the first available as an oral medication, provide rapid testosterone suppression with no initial surge
• provides:
  • rapid and sustained testosterone suppression
  • most adverse events (e.g. hot flush) are consistent with testosterone suppression
  • based on a descriptive analysis without formal adjudication, has a reduced risk of major adverse cardiac events compared with leuprolide

NICE states (2):

• Relugolix is recommended, within its marketing authorisation, as an option for treating prostate cancer in adults:
  • with advanced hormone-sensitive prostate cancer
  • alongside radiotherapy for high-risk localised or locally advanced hormone-sensitive prostate cancer
  • as neoadjuvant treatment before radiotherapy for high-risk localised or locally advanced hormone-sensitive prostate cancer

The NICE committee noted (2):

• "...Clinical trial evidence suggests that relugolix is better at reducing testosterone to levels that stop cancer growth in the long term, and reduces the risk of serious cardiovascular events, compared with leuprolide..."

Reference:

1. Shirley M. Relugolix: A Review in Advanced Prostate Cancer. Target Oncol. 2023 Mar;18(2):295-302.
2. NICE (August 2024). Relugolix for treating hormone-sensitive prostate cancer