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Most men receive darolutamide at full, planned dose in pivotal nonmetastatic CRPC trial


The ad hoc analysis also examined PSA response in the pivotal phase 3 ARAMIS trial.

Over 97% of men with nonmetastatic castration-resistant prostate cancer (CRPC) received the full, planned dose of darolutamide (Nubeqa) in the pivotal phase 3 ARAMIS trial, according to an ad hoc analysis presented during the 2020 ESMO Virtual Congress.1

The ARAMIS trial randomized patients to androgen-deprivation therapy (ADT) plus either darolutamide at a dose of 600 mg twice daily, or placebo. At the time of the ad hoc analysis, the median time on treatment was 18.5 versus 11.6 months in the darolutamide versus control arms, respectively. At a median follow-up of 14.8 months, 97.2% of patients had been treated with the full, planned dose of darolutamide/ADT compared with 98.4% who received the full ADT dose in the control arm.

Dose modifications were required in 15.2% versus 9.7% of the darolutamide versus control arms, respectively; however, 91.7% and 88.9% of these patients, respectively, were eventually able to return to the full, planned dose.

“In clinical practice, ability to maintain planned dose and schedule are important considerations,” Matthew Smith, MD, PhD, director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center, stated in a press release. “These data support darolutamide's value as a treatment option in men with nonmetastatic CRPC.”

The ad hoc analysis also examined PSA response, defined as a ≥50% decrease in PSA level from baseline. Overall, a PSA response was reached in 83.6% of the darolutamide arm compared with 7.6% of the control arm. The median PSA decrease from baseline was 91.7% versus 31.9%, respectively. Of note, around 95% of the patients who had a >90% decrease in PSA from baseline were metastasis free at 12 months.

The double-blind ARAMIS trial included 1509 patients with nonmetastatic CRPC. Patients were randomized in a 2:1 ratio to receive oral darolutamide plus ADT (n = 955) or placebo plus ADT (n = 554). Patients had an ECOG performance status of 0 to 1. The primary end point of the trial was metastasis-free survival (MFS), with overall survival (OS) as a key secondary end point.

Previously reported findings from the primary analysis of the trial showed a highly significant MFS benefit with darolutamide. The darolutamide regimen reduced the risk of metastases or death by 59% versus ADT alone, with a median MFS of 40.4 months versus 18.4 months, respectively (HR, 0.41; P <.001).2 These results led to the July 2019 FDA approval of darolutamide for the treatment of patients with nonmetastatic CRPC.

Subsequent to the approval, OS data from the ARAMIS trial published in the New England Journal of Medicine showed a 31% reduction in the risk of death with darolutamide plus ADT versus ADT alone.2 At a median follow-up of 29 months, the 3-year OS rates were 83% and 77% in the darolutamide and placebo arms, respectively (HR, 0.69; P = .003).

This OS benefit was reached even though over half (55%) of the patients on the control arm received darolutamide (n = 170) or other subsequent treatments (docetaxel, abiraterone acetate [Zytiga], enzalutamide [Xtandi], sipuleucel-T [Provenge], and cabazitaxel [Jevtana]) after the study was unblinded.

In addition to improving OS, the darolutamide regimen also led to statistically significant delays in the time to first symptomatic skeletal event (HR, 0.48; P = .005), time to pain progression (HR, 0.65; P <.001), and time to initiation of chemotherapy (HR, 0.58; P <.001).


1. Ad Hoc Analysis of ARAMIS Showed a High Percentage (97.2%) of Men with Non-Metastatic Castration-Resistant Prostate Cancer Received Full, Planned Dosing of NUBEQA® (darolutamide). Posted September 21, 2020. Accessed September 30, 2020. https://bit.ly/33iA5vk.

2. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. doi: 10.1056/NEJMoa2001342

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