The randomized, double-blind, placebo-controlled, phase 3 ARASENS trial investigated the efficacy of darolutamide plus docetaxel for patients with metastatic hormone-sensitive prostate cancer (mHSPC) across 286 centers between November 2016 and June 2018. A study published in the Journal of Clinical Oncology examined safety and efficacy from the ARASENS trial for certain subgroups by disease volume and risk.
Maha Hussain, MD, FACP, FASCO, lead author on the study and Deputy Director and leader of the GU Oncology Program at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, provided insight on the ARASENS trial.
“Darolutamide is pretty much what I call a new kid on the block,” noted Dr. Hussain. “It was one of the 3 drugs that were approved in the non-metastatic castration resistance space about two or three years ago. The only other drug that is approved as part of the triplet treatment is abiraterone with prednisone.”
During the ARASENS trial, 1305 patients with mHSPC were randomly assigned 1:1 to receive darolutamide or placebo plus androgen-deprivation therapy (ADT) with docetaxel. A total of 1005 (77%) patients had high-volume disease, while 912 (70%) patients had high-risk disease.
“The overall survival was the primary endpoint, and there were several secondary endpoints that we looked at that are clinically important, including time to castration progression disease and time to pain progression,” said Dr. Hussain.
In patients with high-volume, high-risk, or low-risk disease, darolutamide was found to increase overall survival (OS) versus placebo. In a low-volume subgroup, treatment with darolutamide also demonstrated a survival benefit, and in all disease volume and risk subgroups, darolutamide improved the clinically relevant secondary end points of time to castration-resistant prostate cancer and subsequent systemic antineoplastic therapy versus placebo.
Adverse events (AEs) were similar across treatment groups and subgroups. Grade 3 or 4 AEs occurred in 64.9% of patients who received darolutamide versus 64.2% of placebo patients in the high-volume subgroup and in 70.1% and 61.1%, respectively, in the low-volume subgroup. Most of the common AEs were known toxicities related to docetaxel treatment.
“One potential advantage with darolutamide, I would say, compared to the other AR inhibitors, is it’s side effect profile, which generally is very well tolerated.”
Overall, the study found that treatment with darolutamide, ADT, and docetaxel increased OS and had a similar AE profile among the subgroups consistent with the overall population.