Oncology Overview: Darolutamide, a New-Generation Oral Androgen Receptor Inhibitor


Darolutamide exerts its effects via competitive inhibition of androgen binding.

Darolutamide (Nubeqa; Bayer) is a new-generation oral androgen receptor (AR) inhibitor indicated for patients with non-metastatic castration-resistant prostate cancer.1

Although androgen deprivation therapy is the mainstay of care for patients with advanced hormone-sensitive prostate cancer, most patients will subsequently develop castration-resistant prostate cancer.2 The FDA approved darolutamide in 2019 for these patients. The drug’s novel molecular structure theoretically results in fewer and less severe toxic adverse effects (AEs) than other androgen-receptor inhibitors currently on the market.1,3

Indications and Dosage

Darolutamide is available as a 300 mg oral tablet. The recommended dose is 600 mg administered twice a day with food.1

Patients on darolutamide should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy. Patients may continue treatment with darolutamide until disease progression (assessed radiographically) or unacceptable toxicity occurs.1

If a patient experiences grade 3 toxicity or higher or an intolerable reaction to darolutamide, withhold dosing or reduce the dose to 300 mg twice a day until improvement of symptoms.1 Patients may then resume the standard regimen of 600 mg twice a day. The manufacturer does not recommend dose reduction below 300 mg twice a day.1

Mechanism of Action

The primary targets for treatment in prostate cancer are androgens and androgen receptor signaling pathways.2 Darolutamide exerts its effects via competitive inhibition of this androgen binding, leading to blockade of both:2

  • androgen receptor nuclear translocation
  • androgen receptor-mediated transcription

This then decreases signaling from androgen receptors and reduces overall serum androgen levels.

FDA Approval

The FDA approved darolutamide after review of the phase 3 multinational, randomized, double-blind, placebo-controlled Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial.3 ARAMIS’s primary endpoint was metastasis-free survival, the standard endpoint in trials involving castration-resistant prostate cancer.3

Median metastasis-free survival was 40.4 months in the darolutamide group, compared to 18.4 months in the placebo group (95% CI, P<0.001).3 Darolutamide reduced the risk of metastasis or death from any cause by 59%, a benefit evident across patient subgroups.3


Darolutamide’s most common adverse reactions are fatigue, pain in extremities, and rash (see Table 1).1

Serious AEs occurred in 25% of patients receiving darolutamide and 20% of patients receiving the placebo.1

In ARAMIS, researchers reported that the incidence of AEs was generally similar in the darolutamide and placebo groups.3 Further, after adjustment for treatment duration or observation period, the differences between treatment and placebo groups in the incidences of relevant AEs either decreased or disappeared.3

About the Author

Lisa E Ruohoniemi, PharmD, is a Clinical Staff Pharmacist at LewisGale Hospital, Montgomery Blacksburg, VA.


  1. Nubeqa. Prescribing Information. Bayer; 2021. Accessed October 28, 2021. http://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf .
  2. Fizazi K, Albiges L, Loriot Y, Massard C. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer. Expert Rev Anticancer Ther. 2015;15(9):1007-1017. doi:10.1586/14737140.2015.1081566. Published September 2015. Accessed October 26, 2021.
  3. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2019;380(13):1235-1246. doi:10.1056/NEJMoa1815671. Published February 2019. Accessed October 25, 2021.
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