- The international, randomized phase 3 ARASENS trial evaluated the efficacy and safety of adding darolutamide to androgen-deprivation therapy (ADT) and docetaxel in patients with metastatic, hormone-sensitive prostate cancer
- Overall, survival was significantly better among the 651 patients who received ADT and docetaxel plus darolutamide than the 654 who received ADT and docetaxel plus placebo (HR, 0.68; 95% CI, 0.57–0.80; P<0.001)
- Significant improvements with darolutamide were also observed in time to development of castration-resistant disease, time to pain progression, symptomatic skeletal event–free survival, and certain other secondary endpoints
- The incidence, severity and nature of adverse events were consistent with the established safety profiles of ADT and docetaxel
Darolutamide, an androgen-receptor pathway inhibitor, had potent efficacy against nonmetastatic, castration-resistant prostate cancer in the phase 3 ARAMIS trial. The risk of death was 31% lower among patients who received darolutamide with androgen-deprivation therapy (ADT) than among those who received a placebo with ADT, and rates of adverse events were similar in the two groups.
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More recently, in the randomized, double-blind, placebo-controlled, phase 3 ARASENS trial, a multinational research team observed similar efficacy and safety of darolutamide when it was added to ADT and docetaxel in patients with metastatic, hormone-sensitive prostate cancer.
At 286 centers in 23 countries, 1,306 patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled between November 2016 and June 2018. They were randomized 1:1 to receive either darolutamide (600 mg twice daily with food) or a matching placebo in double-blind fashion. All patients received six cycles of docetaxel.
All patients had to have started ADT (luteinizing-hormone–releasing hormone (LHRH) agonist, LHRH antagonist, or orchiectomy) within 12 weeks before randomization. Treatment with a first-generation antiandrogen was recommended for patients who received LHRH agonists, but it had to be stopped at least four weeks before randomization.
Primary Endpoint: Overall Survival
At the data cutoff of October 25, 2021, the median follow-up for overall survival was 44 months in the darolutamide group and 42 months in the placebo group.
Compared with the placebo, darolutamide was associated with a 32.5% reduction in the risk of death (HR, 0.68; 95% CI, 0.57–0.80; P<0.001). That was true even though 76% of patients in the placebo group received subsequent life-prolonging systemic therapies, primarily androgen-receptor pathway inhibitors.
The four-year overall survival rate was 63% in the darolutamide group and 50% in the placebo group. The survival benefit of darolutamide was consistent across most prespecified subgroups.
Secondary Efficacy Endpoints
Secondary efficacy endpoints were tested hierarchically, and darolutamide was linked to significantly greater benefit than placebo on the first five endpoints:
- Time to development of castration-resistant disease—HR, 0.36
- Time to pain progression—HR, 0.79
- Symptomatic skeletal event–free survival—HR, 0.61
- Time to a first symptomatic skeletal event—HR, 0.71
- Time to initiation of subsequent systemic antineoplastic therapy—HR, 0.39
The incidences of any adverse events, grade 3 to 5 adverse events, and serious adverse events were similar in the darolutamide and placebo groups. There was no more than a two percentage point difference between the treatment arms for the incidence of most adverse events commonly associated with androgen-receptor pathway inhibitors.
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