The investigational androgen receptor inhibitor darolutamide may become a new standard of care for men with high-risk nonmetastatic (M0) castration-resistant prostate cancer (nmCRPC), according to results from the ARAMIS trial.
The interim results from the phase 3 trial was presented at the 2019 Genitourinary Cancers Symposium.
“We believe that darolutamide should become a new standard of care for men with high-risk M0 CRPC,” said Karim Fizazi, MD, PhD, the head of the Department of Cancer Medicine at the Institute Gustave Roussy, in Villejuif, France, in a press release.
“Pain progression was delayed and quality of life was meaningfully preserved with darolutamide compared with placebo.”he added.
The study showed that darolutamide (Bayer) doubled median metastasis-free survival (MFS) (18.4 vs. 40.4 months; hazard ratio [HR], 0.41; P<0.0001) and was associated with a 29% reduction in the risk for death compared with placebo (P=0.045).
Prostate cancer that has not spread to other parts of the body and no longer responds to a medical or surgical treatment that lowers testosterone is called non-metastatic castration-resistant prostate cancer or nmCRPC. The cancer is associated with a high risk for progression and cancer-specific death.
Darolutamide is characterized by low blood–brain barrier penetration, which may result in less central nervous system toxicity and improved tolerability, reveals the researchers. Its high affinity for the androgen receptor has promising in vivo activity and a low potential for drug–drug interactions.
ARAMIS enrolled men with nmCRPC and a prostate-specific antigen (PSA) doubling time of 10 months or less. The investigators stratified patients by PSA doubling time (≤6 months) and whether they had received osteoclast-targeted therapy, and randomly assigned them to receive 1,200 mg darolutamide plus androgen deprivation therapy (n=955) or placebo (n=554) twice daily.
After a median follow-up of 17.9 months, the investigators found darolutamide was associated with a 59% reduced risk for the primary end point of distant metastases or death (HR, 0.41; 95% CI, 0.34-0.50; P<0.0001). At three years, darolutamide was associated with a survival probability of 83% compared to 73% with placebo.
“Darolutamide has a very favorable safety profile,” Dr. Fizazi said. “We didn’t find any increase in side effects, such as falls, fractures, cognitive disorders, seizures and hypertension compared to placebo.” Drug discontinuation rates were similar in the two groups, about 9%. “Grade 3/4 adverse events were rarely observed in the trial, which is an important finding for a vast population of asymptomatic men.”
The study is published in The New England Journal of Medicine.