An international, randomized, double-blind, placebo-controlled, Phase III clinical trial led by scientists at Massachusetts General Hospital (MGH) demonstrated that adding the androgen-receptor inhibitor darolutamide to androgen-deprivation therapy and chemotherapy extended the survival of men with metastatic, hormone-sensitive prostate cancer.

Their study is published in the New England Journal of Medicine in a paper titled, “Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer.”

“Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer,” the researchers wrote. “Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.”

Standard treatment for patients with metastatic, hormone-sensitive prostate cancer includes the addition of either the chemotherapy drug docetaxel or an androgen-receptor pathway inhibitor to androgen-deprivation therapy, with the latter two treatments acting to lower the effects of androgen hormones, such as testosterone. Clinical trials that have combined all three treatments have generated conflicting results.

MGH researchers designed the large, international ARASENS trial and randomly assigned 1,306 patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive the oral androgen-receptor inhibitor darolutamide or placebo, both in combination with androgen-deprivation therapy and docetaxel.

Survival rates in the two groups were compared after 533 patients had died. Patients were followed for a median of approximately three and a half years, and those who received darolutamide had a 32.5% lower risk of dying during that time than patients not taking darolutamide.

The combination of three medications did not result in more toxic effects compared with the combination of androgen-deprivation therapy and docetaxel alone.

“Despite progress in recent years, survival is short for patients with metastatic prostate cancer. Results from ARASENS are an important step forward, and triplet therapy with darolutamide should become a new standard of care for the treatment of patients with metastatic hormone-sensitive prostate cancer,” explained lead author Matthew R. Smith, MD, PhD, director of the Genitourinary Oncology Program at the Mass General Cancer Center and an associate professor of medicine at Harvard Medical School.