What is the recommended treatment for a patient with advanced prostate cancer, specifically using Orgovyx (relugolix)?

Orgovyx (Relugolix) for Advanced Prostate Cancer

Orgovyx (relugolix) is an oral GnRH receptor antagonist approved for advanced prostate cancer that provides rapid testosterone suppression without initial testosterone flare, and should be dosed as 360 mg loading dose on day 1 followed by 120 mg once daily. 1

FDA-Approved Indication and Dosing

• Orgovyx is indicated for treatment of adult patients with advanced prostate cancer 1
• The recommended dosage is a loading dose of 360 mg on the first day followed by 120 mg taken orally once daily at approximately the same time each day 1
• Tablets should be swallowed whole and not crushed or chewed 1
• Can be taken with or without food 1

Clinical Efficacy Evidence

• In the pivotal HERO trial, relugolix achieved sustained castration rates >90% over 48 weeks, demonstrating non-inferiority and exploratory superiority compared to leuprolide depot injections 2
• Relugolix provides rapid testosterone suppression without the initial testosterone surge seen with GnRH agonists 3
• Castration resistance-free survival at 48 weeks was similar between relugolix (74.3%) and leuprolide (75.3%) in men with metastatic disease, with no significant difference (HR 1.03, p=0.84) 4

Cardiovascular Safety Advantage

• Relugolix demonstrated a 54% lower incidence of major adverse cardiovascular events compared to leuprolide acetate (HR 0.46,95% CI 0.24-0.88) 5, 2, 3
• This cardiovascular benefit is particularly important given that androgen deprivation therapy may prolong the QT interval 1

Combination Therapy Compatibility

• Relugolix can be safely combined with next-generation hormonal therapies including abiraterone and apalutamide without affecting efficacy or introducing new safety concerns 6, 7
• When combined with abiraterone (1,000 mg once daily) plus corticosteroid, or apalutamide (240 mg once daily), the safety profile remained consistent with individual drugs 7
• Most adverse events in combination therapy were grade 1 or 2, with hypertension most common with abiraterone and rash most common with apalutamide 7
• Medication adherence rates exceeded 97% in combination therapy studies 7

Common Adverse Reactions

• The most common adverse reactions (≥10%) include hot flush, musculoskeletal pain, fatigue, constipation, and diarrhea 1
• Laboratory abnormalities (≥15%) include increased glucose, triglycerides, ALT, AST, and decreased hemoglobin 1
• The adverse event profile is consistent with testosterone suppression and generally well tolerated 2

Important Drug Interactions

• Avoid co-administration with P-glycoprotein (P-gp) inhibitors; if unavoidable, take Orgovyx first, separate dosing by at least 6 hours, and monitor more frequently for adverse reactions 1
• Avoid co-administration with combined P-gp and strong CYP3A inducers; if unavoidable, increase Orgovyx dose to 240 mg once daily 1

Contraindications and Warnings

• Contraindicated in patients with known severe hypersensitivity to relugolix or any product components 1
• Can cause hypersensitivity reactions including angioedema; withhold for symptoms and discontinue for severe reactions 1
• Orgovyx can cause fetal harm; advise males with female partners of reproductive potential to use effective contraception 1

Clinical Context Within Treatment Guidelines

• For metastatic hormone-sensitive prostate cancer, current guidelines recommend ADT combined with novel androgen receptor pathway inhibitors (abiraterone, enzalutamide, apalutamide, or darolutamide) as standard first-line treatment 5, 8
• Relugolix serves as the androgen deprivation component in these combination regimens 5
• For castration-resistant prostate cancer, treatment options include abiraterone, enzalutamide, docetaxel, cabazitaxel, olaparib (for BRCA1/2 mutations), and 177Lu-PSMA-617 5, 9

Practical Advantages

• Oral administration offers convenience compared to injectable GnRH agonists that require clinic visits every 1-3 months 2, 3
• Faster post-treatment recovery of testosterone levels compared to leuprolide 3
• No initial testosterone flare eliminates the need for anti-androgen co-administration during treatment initiation 3