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An androgen deprivation tablet that works faster than the standard injection, wears off faster when stopped, and halved the rate of heart attacks and strokes.
Luteinising hormone-releasing hormone agonists such as leuprolide cause a testosterone surge before they suppress, which is why an anti-androgen is given alongside them at the start, and they are given as depot injections that cannot be stopped. Relugolix is an oral gonadotrophin-releasing hormone antagonist and has neither problem.
HERO randomised men with advanced prostate cancer 2:1 to relugolix 120 mg orally once daily or leuprolide by injection every 3 months for 48 weeks; 622 received relugolix and 308 leuprolide. Sustained castration through 48 weeks was achieved by 96.7 percent (95 percent confidence interval 94.9 to 97.9) on relugolix against 88.8 percent (84.6 to 91.8) on leuprolide, a difference of 7.9 percentage points (4.1 to 11.8), meeting non-inferiority and then superiority (p<0.001). Every other key secondary endpoint favoured relugolix (p<0.001). Castrate testosterone on day 4 was reached by 56.0 percent on relugolix and 0 percent on leuprolide.
Reversibility was measured in a subgroup of 184 men: mean testosterone 90 days after stopping was 288.4 ng/dL after relugolix and 58.6 ng/dL after leuprolide, which matters for a man having a defined course of hormone therapy alongside radiotherapy and hoping to recover.
The cardiovascular finding is the one that changed prescribing. Major adverse cardiovascular events occurred in 2.9 percent on relugolix and 6.2 percent on leuprolide, hazard ratio 0.46 (95 percent confidence interval 0.24 to 0.88). It is a secondary endpoint in a trial not powered for it, and the comparison is against an agonist rather than against no treatment, so it should be read as the best randomised cardiovascular signal available in androgen deprivation rather than as proof. It is the evidence NICE cited in TA995 when it recommended relugolix.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
930 treated.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Sustained castration through 48 weeksprimary | Relugolix 120 mg orally daily | 622 | 96.7% | - | <0.001 for superiority | link |
| Leuprolide by injection every 3 months | 308 | 88.8% | ||||
| Castrate testosterone on day 4 | Relugolix 120 mg orally daily | 622 | 56% | - | <0.001 | link |
| Leuprolide by injection every 3 months | 308 | 0% | ||||
| Major adverse cardiovascular events | Relugolix 120 mg orally daily | 622 | 2.9% | 0.46 (0.24 to 0.88) | - | link |
| Leuprolide by injection every 3 months | 308 | 6.2% |
Shares SWOG 9346 (intermittent androgen deprivation), Relugolix, PATCH (Prostate Adenocarcinoma Transcutaneous Hormone), Hormone therapy.
Shares Sumitomo Pharma (Myovant), Relugolix, Androgen deprivation & AR pathway inhibitors.
Shares PATCH (Prostate Adenocarcinoma Transcutaneous Hormone), Androgen deprivation therapy (ADT), Metastatic hormone-sensitive prostate cancer, Localised prostate cancer, high and very high risk.
Shares Hormone therapy, Androgen deprivation therapy (ADT), Localised prostate cancer, high and very high risk, Androgen deprivation & AR pathway inhibitors.
Shares Hormone therapy, Androgen deprivation therapy (ADT), Metastatic hormone-sensitive prostate cancer, Androgen deprivation & AR pathway inhibitors.
Shares Hormone therapy, Androgen deprivation therapy (ADT), Localised prostate cancer, high and very high risk, Androgen deprivation & AR pathway inhibitors.
Shares Androgen deprivation therapy (ADT), Castration-resistant prostate cancer (CRPC), Prostate cancer.
Shares Hormone therapy, Androgen deprivation therapy (ADT), Localised prostate cancer, high and very high risk, Androgen deprivation & AR pathway inhibitors.