{"entity":{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","aka":[],"tldr":"Enzalutamide is a second-generation androgen-receptor blocker that stops the receptor binding testosterone, entering the nucleus and switching on genes. It is approved at every stage of advanced prostate cancer, from rising PSA after surgery to castration-resistant disease, and fatigue, falls and memory problems are its main drawbacks.","summary":"Enzalutamide is a second-generation androgen receptor antagonist that blocks ligand binding, nuclear translocation and DNA binding, giving more complete AR blockade than older antiandrogens. It is approved across every stage of advanced prostate cancer: AFFIRM and PREVAIL (mCRPC), PROSPER (nmCRPC), ARCHES and ENZAMET (mHSPC, overall survival benefit; ARCHES OS HR 0.66) and EMBARK (high-risk biochemical recurrence, 2023, metastasis-free survival HR 0.42 with leuprolide). It is the partner in TALAPRO-2 (talazoparib) and the MEVPRO trials (mevrometostat), so the next generation of combinations is built on it. Fatigue, falls and cognitive effects are the main toxicities, which is why darolutamide or apalutamide is sometimes preferred in frail men. For a newcomer, enzalutamide is the most widely used androgen-receptor blocker, from rising PSA after surgery to late-stage disease.","status":"approved","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Enzalutamide","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Enzalutamide"},{"label":"NICE TA712: enzalutamide for treating hormone-sensitive metastatic prostate cancer","url":"https://www.nice.org.uk/guidance/ta712"},{"label":"NICE TA377: enzalutamide for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated","url":"https://www.nice.org.uk/guidance/ta377"},{"label":"NICE TA316: enzalutamide for metastatic hormone-relapsed prostate cancer previously treated with a docetaxel-containing regimen","url":"https://www.nice.org.uk/guidance/ta316"},{"label":"NICE TA580: enzalutamide for hormone-relapsed non-metastatic prostate cancer, not recommended","url":"https://www.nice.org.uk/guidance/ta580"}],"tags":[],"related":[],"cancers":["prostate","salivary-duct-carcinoma","prostate-mhspc","prostate-nmcrpc","prostate-mcrpc","prostate-bcr","tnbc"],"sections":[],"technologies":["androgen-deprivation"],"targets":["androgen-receptor"],"drugs":[],"companies":["astellas","pfizer","zydus"],"institutions":[],"pathways":["ar-signaling"],"terms":["mcrpc-mhspc","prostate-uk-drug-approvals"],"trials":["arches","embark","talapro-2","mevpro-1","nct06629779","nct06520345","nct07028853","nct04076059","nct04446117","nct07611110","nct05422911","nct04986423","nct07287150","nct06228053","nct07230106","nct02960022","nct05367440","nct06991556","nct02861573","nct04557449","nct07198633","nct04104776","nct06702995","nct05914116","nct06863272","nct05112965","nct04821622"],"people":[],"bottlenecks":[],"keyPapers":["paper-prosper-nejm-2018","paper-traina-enzalutamide-ar-tnbc-jco-2018"],"journals":[],"dependsOn":[],"notes":["Four NICE appraisals cover enzalutamide in prostate cancer in England and one of them is a refusal. TA712 recommends enzalutamide with androgen deprivation for hormone-sensitive metastatic prostate cancer. TA377 recommends it for metastatic hormone-relapsed disease before chemotherapy is indicated. TA316 recommends it after docetaxel, and states that use after abiraterone is not covered by that guidance. TA580 does not recommend it for high-risk hormone-relapsed non-metastatic prostate cancer, although apalutamide (TA740) and darolutamide (TA660) are recommended in that population. TA1130 recommends talazoparib with enzalutamide for untreated hormone-relapsed metastatic disease under tight conditions."],"brand":"Xtandi","modality":"Small-molecule AR antagonist","mechanism":"Second-generation AR antagonist blocking ligand binding, nuclear translocation, and DNA binding.","approvals":[{"region":"US","year":2012,"indication":"mCRPC after docetaxel (pre-chemo 2014)"},{"region":"US","year":2018,"indication":"Non-metastatic CRPC"},{"region":"US","year":2019,"indication":"mHSPC (ARCHES)"},{"region":"US","year":2023,"indication":"High-risk biochemical recurrence (EMBARK)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/enzalutamide/","neighbours":{"cancer":[{"id":"apocrine-carcinoma-breast","kind":"cancer","name":"Apocrine carcinoma of the breast","route":"/cancers/apocrine-carcinoma-breast/"},{"id":"prostate-bcr","kind":"cancer","name":"Biochemical recurrence of prostate cancer","route":"/cancers/prostate-bcr/"},{"id":"tnbc-luminal-androgen-receptor","kind":"cancer","name":"Luminal androgen receptor triple-negative breast cancer (LAR)","route":"/cancers/tnbc-luminal-androgen-receptor/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate-nmcrpc","kind":"cancer","name":"Non-metastatic castration-resistant prostate cancer","route":"/cancers/prostate-nmcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"salivary-duct-carcinoma","kind":"cancer","name":"Salivary duct carcinoma","route":"/cancers/salivary-duct-carcinoma/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"}],"company":[{"id":"astellas","kind":"company","name":"Astellas","route":"/companies/astellas/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"zydus","kind":"company","name":"Zydus Lifesciences","route":"/companies/zydus/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"chemical-carcinogenesis-receptor-activation","kind":"pathway","name":"Chemical carcinogenesis - receptor activation","route":"/pathways/chemical-carcinogenesis-receptor-activation/"},{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","route":"/pathways/prostate-cancer-signalling/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"term":[{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","route":"/terms/arpi/"},{"id":"androgen-receptor-positive-tnbc","kind":"term","name":"Androgen receptor-positive triple-negative breast cancer","route":"/terms/androgen-receptor-positive-tnbc/"},{"id":"bipolar-androgen-therapy","kind":"term","name":"Bipolar androgen therapy (BAT)","route":"/terms/bipolar-androgen-therapy/"},{"id":"disease-volume-chaarted","kind":"term","name":"Disease volume (CHAARTED high-volume versus low-volume) and LATITUDE risk","route":"/terms/disease-volume-chaarted/"},{"id":"inflation-reduction-act","kind":"term","name":"Inflation Reduction Act 2022: Medicare drug price negotiation","route":"/terms/inflation-reduction-act/"},{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","route":"/terms/mcrpc-mhspc/"},{"id":"prostate-uk-drug-approvals","kind":"term","name":"Prostate cancer drugs in England: what NICE recommends, and what it refuses","route":"/terms/prostate-uk-drug-approvals/"},{"id":"psa-kinetics","kind":"term","name":"PSA kinetics: PSA doubling time and PSA density","route":"/terms/psa-kinetics/"}],"trial":[{"id":"nct06863272","kind":"trial","name":"A Clinical Study of Ifinatamab Deruxtecan Based Treatment Combinations or as Monotherapy to Treat Metastatic Castrate Resistant Prostate Cancer (mCRPC) (MK-2400-01A/IDeate-Prostate02)","route":"/trials/nct06863272/"},{"id":"nct07198633","kind":"trial","name":"A Clinical Study of QLC5508 and/or QLH12016 in Combination With Other Anti-tumor Therapies in Subjects With Advanced Prostate Cancer","route":"/trials/nct07198633/"},{"id":"nct05914116","kind":"trial","name":"A Phase 1/2a Study of DB-1311/BNT324 in Advanced/Metastatic Solid Tumors","route":"/trials/nct05914116/"},{"id":"nct07226986","kind":"trial","name":"A Phase Ib/II Open-label Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI in Adult Participants With PSMA","route":"/trials/nct07226986/"},{"id":"nct02960022","kind":"trial","name":"A Study for Subjects With Prostate Cancer Who Previously Participated in an Enzalutamide Clinical Study","route":"/trials/nct02960022/"},{"id":"nct06099769","kind":"trial","name":"A Study of Enzalutamide, Enzalutamide in Combination With Mifepristone, or Chemotherapy in People With Metastatic Breast Cancer","route":"/trials/nct06099769/"},{"id":"nct07230106","kind":"trial","name":"A Study of SHR3680, HS-20093 and SHR2554 in Subjects With Prostate Cancer","route":"/trials/nct07230106/"},{"id":"nct04104776","kind":"trial","name":"A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas","route":"/trials/nct04104776/"},{"id":"nct06629779","kind":"trial","name":"A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.","route":"/trials/nct06629779/"},{"id":"nct07287150","kind":"trial","name":"A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer","route":"/trials/nct07287150/"},{"id":"nct05422911","kind":"trial","name":"Abiraterone, Enzalutamide, or Apalutamide in Castrate-sensitive Prostate Cancer.","route":"/trials/nct05422911/"},{"id":"affirm","kind":"trial","name":"AFFIRM","route":"/trials/affirm/"},{"id":"nct04076059","kind":"trial","name":"An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormo","route":"/trials/nct04076059/"},{"id":"nct05112965","kind":"trial","name":"An Extension Study in Participants Previously Enrolled in a Genentech and/or F. 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(MK-3475-365/KEYNOTE-365)","route":"/trials/nct02861573/"},{"id":"nct06228053","kind":"trial","name":"Study of SX-682 Plus Enzalutamide in Men With ARPI-Resistant Metastatic Castration Resistant Prostate Cancer","route":"/trials/nct06228053/"},{"id":"nct04821622","kind":"trial","name":"Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC","route":"/trials/nct04821622/"},{"id":"nct06702995","kind":"trial","name":"Study of XNW5004 Tablet in Combination With Enzalutamide in Subjects With Metastatic Castration-Resistant Prostate Cancer","route":"/trials/nct06702995/"},{"id":"nct04557449","kind":"trial","name":"Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors","route":"/trials/nct04557449/"},{"id":"talapro-2","kind":"trial","name":"TALAPRO-2","route":"/trials/talapro-2/"},{"id":"nct06520345","kind":"trial","name":"The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT 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