What is the role of Orgovyx (relugolix) in the treatment of advanced prostate cancer?

Role of Orgovyx (Relugolix) in Advanced Prostate Cancer Treatment

Orgovyx (relugolix) is a first-line androgen deprivation therapy (ADT) option for advanced prostate cancer, particularly recommended for patients with cardiovascular risk factors due to its significantly lower risk of major cardiovascular events compared to traditional LHRH agonists. 1

Mechanism and Indications

Orgovyx is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist FDA-approved for the treatment of adult patients with advanced prostate cancer 2. Unlike traditional LHRH agonists, Orgovyx:

• Provides rapid testosterone suppression without the initial testosterone flare
• Achieves sustained castration rates >90% over 48 weeks of treatment
• Allows for faster testosterone recovery upon discontinuation
• Has a superior cardiovascular safety profile (54% reduction in major adverse cardiac events compared to leuprolide) 3, 4

Clinical Applications

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Orgovyx represents one of four standards of care for noncastrate metastatic prostate cancer when administered with ADT, alongside docetaxel, abiraterone, enzalutamide, or apalutamide 5. It is particularly valuable in:

• Patients requiring rapid testosterone suppression
• Those with significant cardiovascular comorbidities
• Situations where avoiding testosterone flare is critical

Non-Metastatic Advanced Prostate Cancer

For patients with biochemical recurrence after exhaustion of local therapy options, ADT including Orgovyx may be considered, though the AUA/ASTRO/SUO guidelines note that management of this disease state remains controversial due to limited evidence for optimal treatment approaches 5.

Dosing and Administration

• Initial loading dose: 360mg (three 120mg tablets) on day 1
• Maintenance dose: 120mg orally once daily
• Can be taken with or without food 2

Advantages Over Traditional ADT

1. Cardiovascular Safety: Significantly lower risk of major adverse cardiovascular events (HR 0.46) compared to LHRH agonists 1, 4

2. Oral Administration: Improved convenience compared to injectable ADT options, though this requires attention to compliance 6

3. Rapid Testosterone Recovery: 55% of patients achieved testosterone levels above the lower limit of normal range (>280 ng/dL) or baseline at 90 days after discontinuation 2, 7

4. No Testosterone Flare: Avoids the potential clinical consequences of tumor flare that can occur with LHRH agonists 4

Practical Considerations

Compliance and Cost

Despite high theoretical compliance (94% of days covered in real-world data), cost remains a significant barrier, with 50% of patients citing cost as the reason for not filling their prescription 6.

Combination Therapy

Limited data exists on the safety of Orgovyx in combination with other advanced prostate cancer therapies:

• Safety has been established with radiotherapy 7
• Limited data with enzalutamide (2.7% of patients in HERO trial) and docetaxel (<1.3%) 8
• Safety not established with abiraterone, apalutamide, cabazitaxel, or lutetium Lu 177 vipivotide tetraxetan 8

Adverse Effects

Most common side effects include:

• Hot flushes
• Increased blood sugar and triglyceride levels
• Muscle and joint pain
• Decreased hemoglobin
• Elevated liver enzymes
• Fatigue and gastrointestinal effects 2

Patient Selection Algorithm

1. First-line consideration: Patients with advanced prostate cancer requiring ADT

2. Strongest candidates:

   • Patients with cardiovascular disease or risk factors
   • Those requiring rapid testosterone suppression
   • Patients who prefer oral medication and can afford it
   • Those at risk of complications from testosterone flare

3. Caution/alternative considerations:

   • Patients with compliance concerns
   • Those with financial constraints
   • Patients requiring combination with therapies where safety data is limited

Monitoring

• PSA and testosterone levels to confirm adequate response
• Cardiovascular parameters
• QT interval monitoring in susceptible patients 2

Orgovyx represents an important advancement in ADT for advanced prostate cancer, offering cardiovascular safety advantages while maintaining high efficacy in testosterone suppression.