Final Results from Phase 3 ARAMIS Trial Show Promise for Darolutamide in nmCRPC

The study evaluated the use of darolutamide in men with nonmetastatic, castration-resistant prostate cancer compared with placebo while they continued to receive androgen-deprivation therapy.

Data from the final analysis of the double-blind, placebo-controlled, phase 3 ARAMIS trial of darolutamide (Nubeqa) in men with nonmetastatic, castration-resistant prostate cancer (nmCRPC) found that the percentage of patients who were alive at 3 years was significantly higher among those who received the agent than among those who received placebo.1

The data were published in The New England Journal of Medicine and were also presented as part of the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program, held in May 2020.

“Through ongoing research, we have established the importance of focusing treatments on extending lives and limiting side effects for men living with nmCRPC,” lead study investigator Karim Fizazi, MD, PhD, professor of Medicine at the Institut Gustave Roussy in Villejuif, France, said in a press release.2 “With these encouraging darolutamide results, physicians are further armed to treat based on the multiple needs of this patient population including efficacy, delaying morbidity and treatment tolerability.”

In total, 1509 men were randomized 2:1 to receive either darolutamide (n = 955) or placebo (n = 554) while they continued to receive androgen-deprivation therapy (ADT). Previously published resultsdemonstrated a highly significant improvement in the primary end point of metastasis-free survival (MFS), with a median of 40.4 months with darolutamide plus ADT, compared to 18.4 months for placebo plus ADT (P < .001); however, overall survival (OS) data were not yet mature at the time of the MFS analysis (57% of the required number of events).

Given the positive results observed in the primary end point analysis, the treatment assignments were unblinded and patients in the placebo group were permitted to cross over to receive open label darolutamide treatment. At the time of this final analysis, which was planned to be conducted after approximately 240 deaths had occurred, OS and all other secondary end points were evaluated.

The median follow-up time was 29.0 months. At the time of unblinding of the data, a total of 170 patients who were still receiving placebo crossed over to receive darolutamide and 137 patients who had discontinued placebo before unblinding had occurred received at least 1 other life-prolonging therapy.

OS at 3 years was found to be 83% (95% CI, 80-86) in the darolutamide group compared with 77% (95% CI, 72-81) in the placebo group. Moreover, the risk of death was 31% lower in the darolutamide group than in the placebo group (HR, 0.69; 95% CI, 0.53-0.88; P = .003). In addition, darolutamide was associated with a significant benefit in all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy.

Overall, any grade treatment-emergent adverse events (AEs) at final analysis were generally consistent with the primary analysis of the trial. In the final analysis, any grade AEs occurred in 85.7% who received darolutamide (primary analysis: 83.2%) and 79.2% (primary analysis: 76.9%) who received placebo. Specifically, grade 3 or 4 AEs occurred in 26.3% (primary analysis: 24.7%) who received darolutamide and 21.7% (primary analysis: 19.5%) who received placebo. Further, grade 5 AEs occurred in 4.0% (primary analysis: 3.9%) who received darolutamide and 3.4% (primary analysis: 3.2%) who received placebo.

Serious AEs occurred in 26.1% (primary analysis: 24.8%) receiving darolutamide and in 21.8% (primary analysis: 20.0%) receiving placebo. Importantly, permanent discontinuation of treatment due to AEs was unchanged from the primary analysis, occurring in 9% of patients in both arms of the study.

Notably, darolutamide is currently approved by the FDA, EU, and other global markets for the treatment of men with nmCRPC based on data from this trial. Findings in other regions are also underway or planned.


1. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. The New England Journal of Medicine. doi: 10.1056/NEJMoa2001342

2. New England Journal of Medicine Publishes Final Data for NUBEQA® (darolutamide) Plus Androgen Deprivation Therapy Showing a Statistically Significant Improvement in Overall Survival in Men with Non-Metastatic Castration-Resistant Prostate Cancer [news release]. Whippany, NJ. Published September 9, 2020. Accessed September 14, 2020.

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