Darolutamide Shows OS Benefit With ADT in Updated ARAMIS Trial Findings in Prostate Cancer


A significant improvement in overall survival was observed with darolutamide plus androgen deprivation therapy compared with androgen deprivation therapy alone in men with non-metastatic castration-resistant prostate cancer treated in the phase III ARAMIS trial.

Darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) demonstrated a significant improvement in overall survival (OS) over ADT alone in men with non-metastatic castration-resistant prostate cancer (nmCRPC), according to updated results from the phase III ARAMIS trial released by Bayer.1

In the final analysis of the ARAMIS trial, the addition of darolutamide led to a 31% reduction in the risk of death (HR, 0.69; 95% CI, 0.53-0.88; P = .003) versus placebo. Further, extended follow-up showed durability of the tolerability of treatment with the androgen receptor inhibitor.

“Men with nmCRPC typically do not have cancer symptoms. In selecting a treatment for these patients, my goal as a clinician is to improve their overall survival while limiting side effects and drug interactions,” investigator Karim Fizazi, MD, PhD, professor of medicine at the Institut Gustave Roussy, Villejuif, France, said in a statement. “These data add to the growing evidence for darolutamide as an effective treatment option with proven tolerability that extends patients’ lives and delays cancer symptoms.”

Further findings from the phase III ARAMIS trial will be presented during the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program.

According to the released abstract, the median OS has not yet been reached in either treatment arm but favors the addition of darolutamide.2

The combination also showed benefit in delaying the time to pain progression by an extra 14.9 months over ADT alone (40.3 vs 25.4 months; HR, 0.65; 95% CI, 0.53-0.79; P <.001). The time to initiation of first cytotoxic chemotherapy (HR, 0.58; 95% CI, 0.44-0.76; P <.001) and the time to symptomatic skeletal event (HR, 0.48; 95% CI, 0.29-0.82; P = .005) were both also improved with the addition of darolutamide.

ARAMIS is a randomized, double-blind, placebo-controlled phase III trial that investigated the use of darolutamide in combination with ADT alone in men with nmCRPC and a prostate-specific antigen (PSA) doubling time of 10 months or less. Patients were randomized 2:1 to receive either darolutamide at 600 mg twice daily (n = 955) or placebo (n = 554) plus continuous ADT.

In the primary analysis, the median metastasis-free survival (MFS), the primary end point, was 40.4 months in the darolutamide arm compared with 18.4 months in the ADT-alone arm (HR, 0.41; 95% CI, 0.34-0.50; P <.0001). The median MFS was defined as the time from randomization to the time of first evidence of distant metastasis or death from any cause as confirmed by blinded independent central review.3

Adverse events (AEs), mostly of grades 1 or 2, were observed in 83.2% of patients treated with darolutamide compared with 76.9% treated with ADT alone, and grade 3/4 AEs were reported in 24.7% and 19.5% of patients in the darolutamide and placebo arms, respectively. Grade 5 AEs were seen in 3.9% of patients in the darolutamide arm and in 3.2% of patients in the placebo arm, with 3 deaths (1 in the darolutamide arm and 2 in the placebo arm) considered to be due to treatment. Serious AEs were reported in 24.8% and 20.0% of patients in the investigational and control arms, respectively. The rate of discontinuation due to AEs was similar between the 2 arms at 8.9% in the darolutamide arm and 8.7% in the placebo arm.1

The most common AEs with darolutamide were fatigue or asthenic conditions, back pain, arthralgia, diarrhea, hypertension, and constipation.

Darolutamide was approved by the FDA in July 2019 for the treatment of patients with nmCRPC based on earlier findings from the ARAMIS trial.


1. NUBEQA® (darolutamide) Plus Androgen Deprivation Therapy Showed a Statistically Significant Improvement in Overall Survival with Proven Efficacy and Tolerability in Men with Non-Metastatic Castration-Resistant Prostate Cancer [news release]. Whippany, NJ: Bayer; May 13, 2020. https://bit.ly/2zGrR3D. Accessed May 14, 2020.

2. Fizazi K, Shore ND, Tammela T, et al. Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol. 2020;38(suppl; abstr 5514).

3. Fizazi K, Shore ND, Tammela T, et al; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246. doi: 10.1056/NEJMoa1815671.

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