The FDA has now approved darolutamide (Nubeqa®, Bayer), an androgen receptor antagonist, for the treatment of nonmetastatic castration-resistant prostate cancer (CRPC).
The approval was based on the ARAMIS phase 3 trial (NCT02200614), which enrolled 1,509 patients with nonmetastatic CRPC and a prostate-specific antigen doubling time of 10 months or less. Patients were randomized in a 2:1 ratio to receive darolutamide or placebo along with continued androgen deprivation therapy for a primary end point of metastasis-free survival.
Darolutamide substantially increased median metastasis-free survival compared with placebo (40.4 vs 18.4 months), in addition to producing significant results for the trial's secondary end points of overall survival, time to cytotoxic chemotherapy, time to pain progression, and time to a symptomatic skeletal event.
The most common adverse reactions in patients receiving darolutamide included fatigue, pain in the extremities, and rash. Ischemic heart disease was more common in patients taking darolutamide (4.3%), as was heart failure (2.1%). Of patients receiving darolutamide, 8.9% discontinued treatment due to adverse events, compared with 8.7% of patients receiving placebo. Darolutamide did not increase the incidence of seizures, falls, fractures, cognitive disorder, or hypertension. Adverse events of grade 3 or higher and adverse events affecting more than 5% of patients were experienced at similar rates in the darolutamide and placebo arms. With the exception of fatigue, all adverse events occurred in under 10% of patients in either trial arm.
"Among men with nonmetastatic, castration-resistant prostate cancer, metastasis-free survival was significantly longer with darolutamide than with placebo," comment the researchers in their publication in the New England Journal of Medicine, led by first author Karim Fizazi, MD, PhD, Head of the Department of Cancer Medicine at the Institut Gustave Roussy, Villejuif, France, and Professor of Oncology at the University of Paris. "The incidence of adverse events was similar for darolutamide and placebo."
The recommended dosage of darolutamide is 600 mg in the form of two 300-mg tablets, administered orally twice a day with food.
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