The FDA has approved darolutamide (Nubeqa, Bayer), a nonsteroidal androgen receptor inhibitor, for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).
The agency based its approval on the phase 3 ARAMIS (Androgen Receptor Antagonizing Agent for Metastasis-free Survival) trial, which demonstrated that darolutamide plus androgen deprivation therapy (ADT) was associated with significantly prolonged metastasis-free survival (MFS) compared with placebo plus ADT (median 40.4 vs 18.4 months). The drug as under the FDA’s Priority Review designation, which is reserved for medications that may provide significant improvements in the safety or effectiveness in the treatment of serious diseases.
In the ARAMIS trial, the results of which were published online on February 14 in the New England Journal of Medicine, investigators randomly assigned 1509 nmCRPC patients without metastases from 36 countries 2:1 to darolutamide (600 mg twice daily with food) or placebo. Meanwhile, patients continued taking androgen deprivation therapy (luteinizing hormone-releasing hormone agonist or antagonist).
Darolutamide-treated patients had a significant 59% decreased risk of metastasis compared with placebo recipients. With regard to secondary endpoints, darolutamide decreased the risk of death by 29%. It also decreased the risk of pain progression by 35%.
The median MFS found with darolutamide in the ARAMIS trial is similar to that observed with the nonsteroidal androgen receptor inhibitors enzalutamide and apalutamide. In the phase 3 PROSPER trial, the median MFS was 36 months for enzalutamide vs 14.7 months for placebo. In the phase 3 SPARTAN (Selective Prostate Androgen Receptor Targeting with ARN-509) trial, the median MFS was 40.4 months for apalutamide vs 16.2 months with placebo.
In an interview with Renal & Urology News during the Genitourinary Cancers Symposium in San Francisco in February, lead investigator Karim Fizazi, MD, PhD, of Institut Gustave Roussy, Université Paris-Sud, Villejuif, France, who presented study findings at the meeting, emphasized that darolutamide has a much better safety profile compared with enzalutamide and apalutamide. “This is very important because we’re talking about an asymptomatic population of men. … We can maintain their quality of life,” Dr Fizazi said. Darolutamide, he noted, does not penetrate the blood-brain barrier, which probably explains why he and his team did not observe some of the side effects seen with apalutamide and enzalutamide, such as cognitive impairment and fatigue. Unlike enzalutamide and apalutamide, darolutamide was not associated with a higher risk of falls and fractures, which is probably due to central nervous system toxicity.