Darolutamide for Non-Metastatic Castration-Resistant Prostate Cancer

May 11, 2020

In July 2019, the FDA approved darolutamide (Nubeqa, Bayer) for men with prostate cancer that has not spread (ie, nonmetastatic) and no longer responds to medical or surgical treatment that lowers testosterone (ie androgen deprivation therapy).


In July 2019, the FDA approved darolutamide (Nubeqa, Bayer) for men with prostate cancer that has not spread (ie, nonmetastatic) and no longer responds to medical or surgical treatment that lowers testosterone (ie androgen deprivation therapy).1 Darolutamide is an androgen-receptor inhibitor that competitively inhibits androgen binding, androgen receptor nuclear translocation, and androgen receptor-mediated transcription.1


Approval of darolutamide was based on the results of the ARAMIS trial, a phase 3 randomized, double blind, multi-center study enrolling 1509 patients with non-metastatic castrate resistant prostate cancer.1,2,3 Patients were randomized in a 2:1 ratio to receive darolutamide 600 mg twice daily by mouth or placebo while continuing androgen deprivation therapy.1,2,3 The primary endpoint was metastasis-free survival, which was assessed by radiographic imaging (bone scans, computerized tomorgraphy [CT], and magnetic resonance imaging [MRI] of chest, abdomen, and pelvis). 1,2,3

Eligible patients for the trial were required to have a diagnosis of castration-resistant prostate cancer, a baseline prostate specific antigen (PSA) level of at least 2 ng per milliliter, a prostate specific antigen (PSA) doubling time of 10 months or less, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.2,3  The results indicated a median metastasis-free survival time of 40.4 months in the darolutamide group in comparison with 18.4 months in the placebo group (hazard ratio for metastasis or death in the darolutamide group, 0.41; 95% confidence interval, 0.34 to 0.50; P<0.001).1,2,3


The most common adverse events are fatigue (16%), pain in the extremity (6%), and rash (3%).1 Lab abnormalities included: neutrophil count decrease (20%), aspartate aminotransferase (AST) increase (23%), and bilirubin increase (16%).1

Drug interactions are noted when darolutamide is used with a combined P-glycoprotein plus a strong or moderate cytochrome P450 (CYP)-3A4 inducer or inhibitor.1 Darolutamide also interacts with breast cancer resistant protein (BCRP) substrates.1 Females of childbearing potential and males with female partners of childbearing potential should be advised to use effective contraception during treatment, and for 1 week after the last dose of darolutamide.1

Dosage and Cost                      

In patients with non-metastatic castrate resistant prostate cancer, the recommended dosing for darolutamide is 600 mg (two 300-mg film-coated tablets) taken by mouth twice a day with food (total daily dose [TDD) is 1200 mg]).1 The medication showed be swallowed whole.1 Patients receiving darolutamide should also receive gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.1 If a patient misses a dose, they should take the missed dose as soon as they remember prior to the next to the next schedule dose, and they should not take two doses together.1 Dose adjustments are recommended for patients with severe renal impairment (not on dialysis) or moderate hepatic impairment.1 The recommended dose in these patients is 300 mg by twice a day with food.1

Darolutamide is available as 300-mg film coated tablets. The cost per one 300-mg tablet is $115.50, or $13,860/month.4


1. Darolutamide. Package Insert. Bayer HealthCare Pharmaceuticals Inc; 2019. Accessed November 2, 2019.Available at: http://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf.

2. 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

3. Efficacy and safety study of darolutamide (ODM-201) in men with high-risk nonmetastatic castration-resistant prostate cancer (ARAMIS). ClinicalTrials.Gov. July 25, 2014. Accessed November 2, 2019. https://clinicaltrials.gov/ct2/show/NCT02200614.

4. Darolutamide. Lexi-Drugs.Lexicomp. Wolters KluwerHealth, Inc. Riverwoods, IL. Accessed November 2, 2019