Dosing, Safety, and Pharmacokinetics of Combination Therapy With Darolutamide, Androgen Deprivation Therapy, and Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer in the ARASENS Study
In brief
Darolutamide did not meaningfully alter docetaxel exposure in 1,302 patients
In the ARASENS trial, docetaxel drug levels were generally similar with and without darolutamide, and darolutamide exposure was only 10% lower when given with docetaxel. Most patients completed six docetaxel cycles, with similar rates of dose reduction and discontinuation in both groups. Known docetaxel side effects remained the main reason for changing treatment.
- Journal
- Clinical genitourinary cancer (Q1)
- Published
- 6 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Arash Rezazadeh Kalebasty, Ji Sun, Bertrand Tombal, Maha Hussain, Fred Saad, Karim Fizazi, et al.
- PMID
- 42875365
- DOI
- 10.1016/j.clgc.2026.102663
Why clinicians should know about it
- Picked for Urology (top studies of the week, 18 October 2026): Phase III RCT, darolutamide safe with docetaxel
Abstract
INTRODUCTION: Darolutamide is a highly potent androgen receptor inhibitor, that is structurally different by design. Darolutamide is approved for treatment of metastatic hormone-sensitive prostate cancer in combination with or without docetaxel. We present dosing, safety, and pharmacokinetic analyses of potential drug-drug interactions in patients in the ARASENS study. PATIENTS AND METHODS: ARASENS was an international, randomized, double-blind, phase 3 study in which patients were randomized 1:1 to receive darolutamide 600 mg or placebo in combination with androgen deprivation therapy (ADT) plus docetaxel. RESULTS: In the 1302 treated patients, median treatment duration was longer with darolutamide versus placebo (41.0 vs. 16.7 months), and most patients completed 6 cycles of docetaxel (darolutamide 87.6%; placebo 85.5%). Treatment-emergent adverse events (TEAEs) led to docetaxel dose reduction in 19.9% and 19.5% and discontinuation in 8.0% and 10.3% of darolutamide and placebo recipients, respectively. The most common TEAE leading to docetaxel dose reduction was decreased neutrophil count (darolutamide 5.4%; placebo 6.0%). Granulocyte colony-stimulating factor use was similar in both groups (darolutamide 42.4%; placebo 44.6%) and was mostly administered after the first dose of docetaxel (41.9%; 44.3%). Docetaxel plasma concentration profiles with and without darolutamide were generally overlapping, indicating that darolutamide had no clinically relevant effect on docetaxel pharmacokinetics. Darolutamide exposure was 10% lower with docetaxel than without docetaxel, which is not considered clinically relevant. CONCLUSION: Darolutamide can be administered with docetaxel and ADT without clinically relevant drug-drug interactions between darolutamide and docetaxel. Known docetaxel TEAEs were the most common reason for docetaxel dose modification. TRIAL REGISTRATION NUMBER: NCT02799602 (ARASENS).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.