PMID-32469183 – Relugolix HERO Trial in Advanced Prostate Cancer
Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, et al. (HERO Study Investigators). Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020;382(23):2187-2196.
Quick Reference
| Property | Value |
|---|---|
| PMID | 32469183 |
| DOI | 10.1056/NEJMoa2004325 |
| Year | 2020 |
| Journal | New England Journal of Medicine |
| Study Type | RCT (Phase III) |
| Evidence Level | I |
| Sample | 934 patients with advanced prostate cancer |
| Peptide(s) Studied | Relugolix |
Key Findings
- Sustained castration rate through 48 weeks: 96.7% relugolix vs 88.8% leuprolide (noninferiority and superiority demonstrated)
- Rapid castration by day 4: 56.0% relugolix vs 0% leuprolide
- No testosterone flare with oral relugolix (unlike leuprolide)
- Testosterone recovery at 90 days post-discontinuation: 288.4 ng/dL relugolix vs 58.6 ng/dL leuprolide
- Major adverse cardiovascular events: 2.9% relugolix vs 6.2% leuprolide (HR 0.46)
- Oral administration offers significant convenience over injectable depot formulations
Study Design
Phase III, randomized, open-label, multinational trial (HERO) comparing oral relugolix 120 mg daily (after 360 mg loading dose) versus leuprolide acetate depot 22.5 mg IM every 3 months in 934 men with advanced prostate cancer. Primary endpoint was sustained testosterone suppression to castrate levels through 48 weeks. Key secondary endpoints included castration rate at day 4, testosterone recovery, PSA response, and cardiovascular safety.
Limitations
- Open-label design
- Oral daily dosing requires adherence (vs quarterly injection)
- Follow-up limited to 48 weeks
- Not powered for overall survival or cancer-specific outcomes
- Cost difference not addressed
Clinical Relevance
The HERO trial was practice-changing as it established relugolix (Orgovyx) as the first oral androgen deprivation therapy for advanced prostate cancer. Its key advantages include: (1) no testosterone flare, (2) rapid onset of action, (3) faster testosterone recovery after discontinuation enabling intermittent ADT, and (4) a potentially improved cardiovascular safety profile (HR 0.46 for MACE). This led to FDA approval in December 2020 and represented a paradigm shift toward oral GnRH antagonism.
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#research #RCT #peptide #sexual-health #evidence-level-I