Dr Tombal on the Pharmacokinetics of Darolutamide Plus Docetaxel in mHSPC

Bertrand Tombal, MD, PhD, professor of Physiology, chair of the Division of Urology, the Université catholique de Louvain, the Cliniques universitaires Saint-Luc, in Brussels, Belgium, discusses the pharmacokinetics of darolutamide (Nubeqa) plus docetaxel in metastatic hormone-sensitive prostate cancer (mHSPC).

The phase 3 ARASENS trial (NCT02799602) evaluated the efficacy and safety of darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel vs ADT and docetaxel alone in patients with mHSPC. Findings showed that darolutamide plus ADT/docetaxel reduced the risk of death by 32.5% vs ADT and docetaxel alone (HR, 0.68; 95% CI, 0.57-0.80; P < .0001). In updated data presented at the 2023 Genitourinary Cancers Symposium, investigators reported overall survival data observed in subgroups of patients by disease volume and disease risk showed that the combination reduced the risk of death by about 30% across all subgroups.

Investigators have been attempting to combine docetaxel various agents for the treatment of castration-resistant prostate cancer setting for years; however, none of these trials were positive, Tombal notes. One of the reasons prior combination failed to demonstrate benefit was the additional agent would interfere with the pharmacokinetics of docetaxel, resulting in a decrease of efficacy of either docetaxel or the drug that is being tested, Tombal adds. Since darolutamide has a favorable drug interaction profile, it was a logical choice to test in combination with docetaxel in this setting, and these updated data from ARASENS confirm that hypothesis, Tombal expands.

Investigators showed that darolutamide does not impact the pharmacokinetics of docetaxel, and docetaxel does not impact those of darolutamide, Tombal continues, noting that no added toxicity or inferior efficacy were observed with the combination of the drugs. Although these data only add additional confirmation to the efficacy previously reported from the trial, it was important to report this information, Tombal concludes.