{"entity":{"id":"hero","kind":"trial","name":"HERO","aka":["HERO","HERO trial","relugolix against leuprolide"],"tldr":"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.","summary":"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.\n\nHERO 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.\n\nReversibility 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.\n\nThe 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.","status":"positive","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT03085095","url":"https://clinicaltrials.gov/study/NCT03085095"},{"label":"HERO (New England Journal of Medicine 2020)","url":"https://doi.org/10.1056/NEJMoa2004325"},{"label":"NICE TA995: relugolix for treating hormone-sensitive prostate cancer","url":"https://www.nice.org.uk/guidance/ta995"}],"tags":[],"related":[],"cancers":["prostate","prostate-mhspc","prostate-high-risk"],"sections":[],"technologies":["androgen-deprivation"],"targets":[],"drugs":["relugolix","leuprolide"],"companies":["sumitomo-pharma"],"institutions":[],"pathways":[],"terms":["adt","hormone-therapy","castration-resistance"],"trials":["patch-transdermal-oestradiol","swog-9346"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03085095","phase":"3","setting":"Advanced prostate cancer needing androgen deprivation: oral relugolix 120 mg once daily against leuprolide by injection every 3 months for 48 weeks, randomised 2:1, with sustained testosterone suppression below 50 ng/dL through 48 weeks as the primary endpoint","sponsor":"Myovant Sciences","result":"Sustained castration through 48 weeks in 96.7 against 88.8 percent (difference 7.9 percentage points, 95 percent confidence interval 4.1 to 11.8, superior, p<0.001); castrate testosterone by day 4 in 56.0 against 0 percent; major adverse cardiovascular events 2.9 against 6.2 percent (hazard ratio 0.46, 0.24 to 0.88).","yearReported":2020,"enrolled":930,"enrolledBasis":"treated","enrolledNote":"622 men received relugolix and 308 received leuprolide, a 2:1 randomisation; the figure quoted is the treated population reported in the primary publication.","outcomes":[{"endpoint":"Sustained castration through 48 weeks","primary":true,"unit":"%","arms":[{"name":"Relugolix 120 mg orally daily","n":622,"value":96.7},{"name":"Leuprolide by injection every 3 months","n":308,"value":88.8}],"p":"<0.001 for superiority","source":"https://doi.org/10.1056/NEJMoa2004325"},{"endpoint":"Castrate testosterone on day 4","unit":"%","arms":[{"name":"Relugolix 120 mg orally daily","n":622,"value":56},{"name":"Leuprolide by injection every 3 months","n":308,"value":0}],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa2004325"},{"endpoint":"Major adverse cardiovascular events","unit":"%","arms":[{"name":"Relugolix 120 mg orally daily","n":622,"value":2.9},{"name":"Leuprolide by injection every 3 months","n":308,"value":6.2}],"hr":0.46,"ci":[0.24,0.88],"source":"https://doi.org/10.1056/NEJMoa2004325"}],"replication":"Not independently replicated. PATCH, comparing transdermal oestradiol with a luteinising hormone-releasing hormone agonist in 1,694 men, found no difference in cardiovascular events (hazard ratio 1.11, 0.80 to 1.53), so the cardiovascular advantage reported here is specific to this comparison and should be read cautiously."},"route":"/trials/hero/","neighbours":{"cancer":[{"id":"prostate-high-risk","kind":"cancer","name":"Localised prostate cancer, high and very high risk","route":"/cancers/prostate-high-risk/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"}],"drug":[{"id":"leuprolide","kind":"drug","name":"Leuprolide (leuprorelin) and GnRH agonists","route":"/drugs/leuprolide/"},{"id":"relugolix","kind":"drug","name":"Relugolix","route":"/drugs/relugolix/"}],"company":[{"id":"sumitomo-pharma","kind":"company","name":"Sumitomo Pharma (Myovant)","route":"/companies/sumitomo-pharma/"}],"term":[{"id":"adt","kind":"term","name":"Androgen deprivation therapy (ADT)","route":"/terms/adt/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"hormone-therapy","kind":"term","name":"Hormone therapy","route":"/terms/hormone-therapy/"}],"trial":[{"id":"patch-transdermal-oestradiol","kind":"trial","name":"PATCH (Prostate Adenocarcinoma Transcutaneous Hormone)","route":"/trials/patch-transdermal-oestradiol/"},{"id":"swog-9346","kind":"trial","name":"SWOG 9346 (intermittent androgen deprivation)","route":"/trials/swog-9346/"}]}}