# Darolutamide

Source: https://onco.cc/drugs/darolutamide/  
OnCo record `darolutamide` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Darolutamide is an AR blocker that barely enters the brain, so it causes fewer falls and cognitive side effects; it is approved with and without chemotherapy.

## Summary

Darolutamide is a structurally distinct androgen receptor antagonist with low blood-brain-barrier penetration and activity against the AR F877L resistance mutation. Because little drug reaches the brain it causes fewer falls, fatigue and cognitive side effects than enzalutamide, which matters for older men and those on many medicines. ARAMIS (nmCRPC) showed an overall survival benefit; ARASENS proved triplet therapy with ADT plus docetaxel in mHSPC (OS HR 0.68, 4-year OS 62.7% versus 50.4%); ARANOTE supported the 2025 approval with ADT alone in mHSPC. Whether all men with metastatic hormone-sensitive disease need the chemotherapy component, or only those with high-volume disease, is still argued. For a newcomer, darolutamide is the AR blocker that barely enters the brain, approved with and without chemotherapy.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-06
- Brand: Nubeqa
- Modality: Small-molecule AR antagonist
- Mechanism: Structurally distinct AR antagonist, low blood-brain-barrier penetration, active against AR F877L.
- Approvals: US 2019: Non-metastatic CRPC; US 2022: mHSPC with docetaxel (ARASENS); US 2025: mHSPC with ADT alone (ARANOTE)

## Notes

- Three NICE appraisals cover darolutamide in England. TA660 recommends it with androgen deprivation for hormone-relapsed prostate cancer at high risk of metastasis. TA903 recommends it with androgen deprivation and docetaxel for hormone-sensitive metastatic prostate cancer. TA1109 recommends it with androgen deprivation alone for hormone-sensitive metastatic prostate cancer only if docetaxel is not suitable, and adds an explicit instruction to use the least expensive of the suitable options, including apalutamide with androgen deprivation.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Darolutamide
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Darolutamide
- NICE TA660: darolutamide with androgen deprivation therapy for treating hormone-relapsed non-metastatic prostate cancer: https://www.nice.org.uk/guidance/ta660
- NICE TA903: darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer: https://www.nice.org.uk/guidance/ta903
- NICE TA1109: darolutamide with androgen deprivation therapy for treating hormone-sensitive metastatic prostate cancer: https://www.nice.org.uk/guidance/ta1109

## Connected records

- cancers: [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Non-metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-nmcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/)
- companies: [Bayer](https://onco.cc/companies/bayer/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Prostate cancer (KEGG map)](https://onco.cc/pathways/prostate-cancer-signalling/)
- terms: [Disease volume (CHAARTED high-volume versus low-volume) and LATITUDE risk](https://onco.cc/terms/disease-volume-chaarted/), [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://onco.cc/terms/mcrpc-mhspc/), [Prostate cancer drugs in England: what NICE recommends, and what it refuses](https://onco.cc/terms/prostate-uk-drug-approvals/), [PSA kinetics: PSA doubling time and PSA density](https://onco.cc/terms/psa-kinetics/)
- trials: [A Phase 1b/2a Study of Pocenbrodib as Monotherapy and in Combination With Darolutamide in Participants With mCRPC](https://onco.cc/trials/nct06785636/), [A Study of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer](https://onco.cc/trials/nct06568094/), [A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) and Placebo Given With ADT in Men With Hormone Sensitive Prostate Cancer](https://onco.cc/trials/nct05794906/), [A Study to Learn How Well a Combination of Darolutamide and Androgen Deprivation Therapy (ADT) Works as a Treatment Before Surgery for Men Who Have Hi](https://onco.cc/trials/nct07450599/), [ARAMIS](https://onco.cc/trials/aramis/), [ARANOTE](https://onco.cc/trials/aranote/), [ARASENS](https://onco.cc/trials/arasens/), [AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)](https://onco.cc/trials/nct07611110/), [Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer](https://onco.cc/trials/nct06190899/), [Neoadjuvant Darolutamide Alone or in Combination With Standard Therapy for Stage II-IIIA, AR+, TNBC](https://onco.cc/trials/nct07016399/), [Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer](https://onco.cc/trials/nct05367440/), [Study to Continue Treatment With Darolutamide in Patients Who Have Been Participating in Previous Darolutamide Studies Supported by Bayer](https://onco.cc/trials/nct04464226/), [TulmiSTAR-02: A Phase I/II Open-label Study of Tulmimetostat in Combination With Darolutamide vs. Darolutamide, and Tulmimetostat With Abiraterone in ](https://onco.cc/trials/nct07190300/)
- key papers: [ARAMIS: darolutamide in non-metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-aramis-nejm-2019/), [ARASENS: darolutamide added to androgen deprivation and docetaxel in metastatic hormone-sensitive prostate cancer](https://onco.cc/key-papers/paper-arasens-nejm-2022/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)

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