On August 5, 2022, the U.S. Food and Drug Administration approved darolutamide (Nubeqa®) in combination with docetaxel in adults with metastatic hormone-sensitive prostate cancer (mHSPC). The approval was based on clinical trial findings demonstrating that the agent improved overall survival and significantly delayed time to pain progression compared to placebo.
Androgen receptor inhibitor
Mechanism of Action
Darolutamide competitively inhibits androgens from binding to their receptors, restricting AR nuclear translocation as well as AR-mediated transcription, which decreases cancer cell proliferation and tumor growth.
Adults with mHSPC or nonmetastatic castration-resistant prostate cancer (nmCRPC). Darolutamide is indicated in combination with docetaxel in mHSPC only.
600 mg orally twice daily until patients experience disease progression or unacceptable toxicity
Take two tablets (300 mg each) by mouth with food, twice daily. For patients with mHSPC receiving combination treatment with docetaxel, administer the first docetaxel cycle within six weeks of starting darolutamide.
- nmCRPC: More than 2% of patients experienced increased AST or bilirubin, decreased neutrophil count, fatigue, pain in extremity, and rash.
- mHSPC: More than 10% of patients reported constipation, decreased appetite, rash, hemorrhage, weight gain, and hypertension. More than 30% experienced anemia, hyperglycemia, decreased lymphocyte or neutrophil count, increased AST or ALT, and hypocalcemia.
The package insert indicates warnings and precautions for ischemic heart disease, seizures, and embryo-fetal toxicity.
Concomitant use with darolutamide may increase toxicities from breast cancer–resistance protein (BCRP) substrates. Concomitant use of darolutamide with a combined P-gp and strong or moderate CYP3A4 inducer may decrease darolutamide activity. Concomitant use of darolutamide with a combined P-gp and strong CYP3A4 inhibitor may increase risk of adverse reactions. See the sidebar for more details.
Administer a gonadotropin-releasing hormone analog (e.g., leuprolide, goserelin) concurrently or verify that patients have had a bilateral orchiectomy. Darolutamide has several drug-drug interactions (see sidebar); assess patients regularly for other medications or supplements. Darolutamide dosing may be continued even if a docetaxel cycle is delayed, interrupted, or discontinued.
Swallow the tablets whole with food. Do not take two doses together to make up for a missed dose. If you or your partner is of reproductive potential, use effective contraception during treatment and for at least one week following your last dose. Darolutamide may impair fertility, and you may be at increased risk for seizure. Avoid activities where a sudden loss of consciousness could harm yourself or others.
Oncology nurses can use ONS’s patient education sheet for darolutamide to guide their patient discussions.
In the drug’s clinical trials, no differences in safety or efficacy were found in patients older than age 65 compared to younger patients. Patients with severe renal or moderate hepatic impairment should receive a reduced dose. Because of the possible impact on fertility, discuss preservation options with patients of reproductive potential prior to initiating treatment.
Educate patients about proper storage and safe handling at home, particularly if caregivers assist administration.
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