Treatment with the investigational agent darolutamide (Bayer/Orion) significantly extended metastasis-free survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), results from the phase 3 ARAMIS trial show.
Darolutamide prolonged metastasis-free survival to 40.4 months, which was 22 months longer than observed with placebo, and the risk of metastasis or death from any cause was reduced by 59%. This was seen across all patient subgroups, including those with lower-risk disease.
Based on these findings, lead author Karim Fizazi, MD, PhD, head of the Department of Cancer Medicine at the Institut Gustave Roussy, Villejuif, France, believes that “darolutamide should become the new standard of care,” in this population in the future.
Fizazi presented the results here at the Genitourinary Cancers Symposium (GUCS) 2019; the study was published online February 14 in the New England Journal of Medicine.
Darolutamide is a unique nonsteroidal androgen-receptor antagonist that is structurally distinct from other androgen-receptor inhibitors, and consists of two pharmacologically active diastereomers. Data from preclinical studies suggested that it may have fewer and less severe toxicities than other agents due to its low penetration of the blood–brain barrier, and low binding affinity for γ-aminobutyric acid type A receptors.
Fizazi explained that previous phase 1 and II trials in men with nmCRPC demonstrated significant antitumor activity and a satisfactory side-effect profile, and those findings led to the current study
The ARAMIS trial is a double-blind, placebo-controlled phase III trial that randomized 1509 men with nmCRPC to receive darolutamide 600 mg (two 300 mg tablets) twice daily or placebo, while continuing on androgen deprivation therapy.
All patients had a baseline prostate-specific antigen (PSA) level of at least 2 ng/mL and a PSA doubling time of 10 months or less, and were stratified by PSA doubling time (≤6 months or >6 months) and use of osteoclast-targeted therapy.
The primary endpoint was metastasis-free survival (MFS), with independent central review of radiographic imaging every 16 weeks. MFS is a relatively new endpoint in prostate cancer trials, introduced in the last few years because it can be measured more quickly than the ultimate endpoint — overall survival — which can require years of follow-up; it has already been used for new drug approvals, but there have also been questions raised about this surrogate endpoint.
In the ARAMIS trial, the median MFS was 40.4 months in the darolutamide group as compared with 18.4 months for placebo group (hazard ratio [HR] for metastasis or death in the darolutamide group, 0.41; 95% confidence interval [CI], 0.34 – 0.50; P < .001). The benefit remained consistent across all subgroups, including the subgroup of patients with lower-risk disease.
–GDMeds, an India Pharmacy Service company
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