Darolutamide Approved for Treatment of Metastatic Hormone-Sensitive Prostate Cancer

The FDA has approved darolutamide (Nubeqa®, Bayer HealthCare Pharmaceuticals Inc.) in combination with docetaxel for adult patients with metastatic hormone-sensitive prostate cancer (mHSPC).

“Standard treatment for patients with metastatic, hormone-sensitive prostate cancer includes the addition of either docetaxel or an androgen-receptor pathway inhibitor to androgen-deprivation therapy,” wrote Matthew Smith, MD, PhD, Director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center, and colleagues in their report of the ARASENS trial (NCT02799602), on which the approval was based. “Darolutamide is a structurally distinct androgen-receptor inhibitor with low blood–brain barrier penetration and limited potential for clinically relevant drug–drug interactions.”

The safety and efficacy of darolutamide was assessed in the phase 3, double-blind, placebo-controlled trial, which randomized 1,306 patients in a 1:1 ratio to receive either darolutamide 600 mg orally, twice a day in combination with 75 mg/m2 of docetaxel administered intravenously every three weeks for up to six cycles, or placebo plus docetaxel. Patients concurrently received a gonadotropin-releasing hormone analog or underwent a bilateral orchiectomy. The primary end point was overall survival, with a key secondary end point of time-to-pain progression.

With a median follow-up of 43.7 months for patients receiving darolutamide plus docetaxel and 42.4 months for those receiving placebo plus docetaxel, overall survival was not reached in the darolutamide arm compared with a median overall survival of 48.9 months in the placebo arm. At four years, overall survival was seen to be 62.7% in the darolutamide arm compared with 50.4% in the placebo arm. Additionally, it was noted that time-to-pain progression saw a significantly longer delay in occurrence in the darolutamide arm compared with the placebo arm (hazard ratio 0.79).

The most common adverse reactions experienced by ≥10% of patients receiving darolutamide plus docetaxel were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities experienced by ≥30% of patients were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), and hypocalcemia.

“The results of our trial support the use of darolutamide in combination with androgen-deprivation therapy and docetaxel in patients with metastatic, hormone-sensitive prostate cancer,” concluded Dr. Smith and colleagues in their report. “The addition of darolutamide to androgen-deprivation therapy and docetaxel increased overall survival, and improvements were observed with respect to key secondary end points, with no increase in adverse events.”

The recommended dose of darolutamide for patients with mHSPC is two 300 mg tablets taken orally, twice daily, with food until unacceptable toxicity or disease progression, in combination with docetaxel, which should be administered 75 mg/m2 intravenously every three weeks for up to six cycles. After the start of treatment with darolutamide, the first dose of docetaxel should be administered within six weeks.

For More Information

Smith MR, Hussain M, Saad F, et al (2022). Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med, 386(12):1132-1142. DOI:10.1056/NEJMoa2119115

Clinicaltrials.gov (2022). ODM-201 in addition to standard ADT and docetaxel in metastatic castration sensitive prostate cancer (ARASENS). NLM identifier: NCT02799602.

Nubeqa® (darolutamide) prescribing information (2022). Bayer HealthCare Pharmaceuticals Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212099s002lbl.pdf

US Food and Drug Administration (2022). FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-tablets-metastatic-hormone-sensitive-prostate-cance

Image credit: Yale Rosen. Licensed under CC BY-SA 2.0

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