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In the prior primary analysis of industry-funded, randomized, placebo-controlled, phase III ARAMIS trial (NEJM JW Oncol Hematol May 2019 and N Engl J Med 2019; 380:1235), darolutamide was shown to prolong metastasis-free survival at a median follow-up of 17.9 months in 1509 patients with nonmetastatic castration-resistant prostate cancer (defined as a prostate-specific antigen doubling time of <10 months and no evidence of metastases). Now, investigators report results of a prespecified final analysis of the ARAMIS study at a median follow-up of 29.0 months. Patients were randomized 2:1 to receive darolutamide (600 mg twice daily) or placebo.
Overall survival at 3 years was 83% in the darolutamide group and 77% in the placebo group. Darolutamide reduced the risk for death by 31%, compared with placebo (hazard ratio, 0.69; P=0.003) and significantly prolonged time to first symptomatic skeletal event and time to first use of chemotherapy. Incidence of adverse events after initiation of treatment was similar between the two groups.
Fizazi K et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med 2020 Sep 10; 383:1040. (https://doi.org/10.1056/NEJMoa2001342)
Comment
Three novel antiandrogens — enzalutamide, apalutamide, and darolutamide — have recently been approved by the FDA for the management of men with nonmetastatic castration-resistant prostate cancer. All three agents studied in this setting have now demonstrated improvements in both metastases-free and overall survival. When one reviews each study in isolation, the toxicity profile of darolutamide compared with placebo appears highly favorable.