Using Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer

Pharmacy Practice in Focus: OncologyFebruary 2022
Volume 4
Issue 1

The drug's novel molecular structure may result in fewer toxic adverse effects.

Darolutamide (Nubeqa; Bayer) is a new-generation oral androgen receptor inhibitor indicated for patients with nonmetastatic 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 In 2019, the FDA approved darolutamide for these patients; the novel molecular structure of darolutamide 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

Available as a 300-mg oral tablet, darolutamide is recommended to be administered to patients at a dose of 600 mg twice a day with food. 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, which would be assessed radiographically, or unacceptable toxicity occurs.1

If a patient experiences grade 3 toxicity or higher or an intolerable reaction to darolutamide, it is important to withhold dosing or reduce the dose to 300 mg twice a day until the symptoms improve. Upon symptom improvement, patients can 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

In prostate cancer, the primary targets for treatment are androgens and androgen receptor signaling pathways. Darolutamide exerts its effects via competitive inhibition of this androgen binding, leading to the blockade of both the androgen receptor nuclear translocation and the androgen receptor–mediated transcription. This decreases signaling from androgen receptors and reduces overall serum androgen levels.2

FDA Approval

The FDA's approval of darolutamide was based on a review of the results from the phase 3 multinational, randomized, double-blind, placebo-controlled ARAMIS trial (NCT02200614).3 The study’s primary end point was metastasis-free survival, which is the standard end point in trials involving castration-resistant prostate cancer.3

During the study, median metastasis-free survival was 40.4 months in the darolutamide group versus 18.4 months in the placebo group (HR 0.41; 95% CI, 0.34 to 0.50; P<0.001). Darolutamide reduced the risk of metastasis or death from any cause by 59%, a benefit evident across patient subgroups.3

Assessing AEs

During treatment with darolutamide, the most common AEs experienced by patients are fatigue, pain in extremities, and rash (TABLE).1

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

In the ARAMIS trial, investigators reported that the incidence of AEs was generally similar in the darolutamide and placebo groups. 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

Lisa E. Ruohoniemi, PharmD, is a clinical staff pharmacist at LewisGale Hospital Montgomery in Blacksburg, Virginia.


  1. Nubeqa. Prescribing Information. Bayer; 2021. Accessed October 28, 2021. http://
  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
  3. Fizazi K, Shore N, Tammela TL, et al; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246. doi:10.1056/ NEJMoa1815671
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