A year ago, initial results from the double-blind, multicenter, randomized phase III ARAMIS clinical trial evaluating the efficacy and safety of darolutamide, a structurally unique androgen-receptor antagonist, in men with nonmetastatic castration-resistant prostate cancer, were published in The New England Journal of Medicine.1 A full summary of the initial results is included in this issue on page 21.
In brief, the initial results showed that darolutamide significantly prolonged metastasis-free survival vs placebo in the study population by 22 months. The study also found that darolutamide had a favorable safety profile and was not associated with an increased incidence of adverse events common with other androgen-receptor inhibitors. Darolutamide also proved to have a low potential for drug-drug interactions with medications used to treat comorbidities in patients with nonmetastatic castration-resistant prostate cancer.
Based on the ARAMIS study findings, on July 30, 2019, the U.S. Food and Drug Administration (FDA) approved darolutamide for the treatment of nonmetastatic castration-resistant prostate cancer.
Final Analysis: Overall Survival
Karim Fizazi, MD, PhD
During the ASCO20 Virtual Scientific Program, lead author of the ARAMIS trial, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Université Paris-Sud, Villejuif, France, presented data from the final analysis the phase III ARAMIS clinical trial.2 According to Dr. Fizazi, final analysis of the study was conducted after 254 deaths were observed (148/955 = 15.5% of patients receiving darolutamide and 106/554 = 19.1% of patients receiving placebo). In addition, darolutamide was associated with a statistically significant 31% reduction in the risk of death compared with placebo (HR = 0.69; 95% CI = 0.53–0.88; two-sided P = .003). The overall survival rate at 3 years was 83% (95% CI = 80%–86%) in the darolutamide group and 77% (95% CI = 72%–81%) in the placebo group. And the overall survival benefit was observed despite more than half of the patients in the placebo group receiving subsequent darolutamide or other life-prolonging therapies.
Additional Clinical Benefits
Darolutamide also significantly delayed the time to pain progression, the time to first cytotoxic chemotherapy, and the time to first symptomatic skeletal event, as reported in the final analysis. “Darolutamide, therefore, provides clinical benefits in addition to prolonging survival for men with nonmetastatic castration-resistant prostate cancer for whom the development of metastasis can cause cancer-related symptoms that affect their daily lives or impose the burden of additional treatments,” Dr. Fizazi said during his presentation.
All exploratory endpoints tested at this analysis favored darolutamide for delaying disease progression and additional treatment. With extended follow-up, the safety profile of darolutamide at final analysis was favorable and consistent with the findings in the primary analysis of the study.
Disclosure: Dr. Fizazi has received honoraria from Astellas Pharma, Janssen, Merck, and Sanofi; has served as a consultant or advisor to Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, CureVac, ESSA Pharma, Janssen Oncology, Orion Pharma GmbH, Roche/Genentech, and Sanofi; and has received travel and accommodation expenses from Amgen and Janssen.
1. Fizazi K, et al: Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 380:1235-1246, 2019.
2. Fizazi K, et al: Overall survival results of phase III ARAMIS study of darolutamide added to androgen deprivation therapy for nonmetastatic castration-resistant prostate cancer. ASCO20 Virtual Scientific Program. Abstract 5514.