FDA Approves Darolutamide Combo for Metastatic Hormone-Sensitive Prostate Cancer

On Friday, the FDA approved darolutamide with docetaxel to treat patients with metastatic hormone-sensitive prostate cancer (mHSPC), following trial results that showed a 32% reduction in the risk of death compared with docetaxel alone. Results were announced by the FDA and Bayer, maker of darolutamide.

Darolutamide, sold as Nubeqa, is an androgen receptor inhibitor, which works to limit prostate cell growth by preventing the binding of hormones, or androgens, to proteins known as androgen receptors. The drug is being studied in several forms of prostate cancer and was previously approved to treat nonmetastatic castration-resistant prostate cancer.

The FDA’s approval for the new indication came through its Real-Time Oncology Review program; the application for the new indication received priority review status on May 3. This follows presentation of the phase 3 results from the ARASENS trial, which were presented earlier this year at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO). Results also appeared in The New England Journal of Medicine.

Data from the American Cancer Society show that prostate cancer is the second leading cancer-related cause of death among men in the United States, and up to a third of patients develop metastatic disease. According to ASCO, the incidence of mHSPC has increased by 72% in the United States during the past decade, with 1 in 3 patients surviving 5 years or longer. Most progress to castration-resistant prostate cancer.

In the study, patients were randomized to receive either 600 mg of darolutamide orally twice a day plus 75 mg/mg² of docetaxel intravenously every 3 weeks or docetaxel plus placebo. Patients received a gonadotropin-releasing hormone analog concurrently or had a bilateral orchiectomy.

Reports of adverse events (AEs) were similar in both arms. Reactions among the darolutamide arm appearing in more than 10% of patients vs the placebo arm were constipation (23% vs 20%), decreased appetite (19% vs 13%), rash (19% vs 15%), hemorrhage (18% vs 13%), increased weight (18% vs 16%), and hypertension (14% vs 9%). Serious AEs occurred in 45% of patients in the darolutamide arm vs 42% in the placebo arm.

“Nubeqa plus [androgen deprivation therapy] and docetaxel has shown significant benefit in overall survival and a favorable safety profile for patients with metastatic hormone-sensitive prostate cancer,” Matthew Smith, MD, PhD, director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center, said in a statement. The new indication, he said, “is particularly meaningful, as it highlights its proven tolerability and provides a new option for patients.”

“Prostate cancer is the most common cancer among men in the US, with chances of survival decreasing dramatically for those diagnosed with mHSPC compared to localized prostate cancer,” Charles J. Ryan, MD, president and CEO, Prostate Cancer Foundation, said in the statement. “This approval adds a different treatment approach for mHSPC patients and their physicians to choose from.”