Use of concomitant G-CSF in maintaining efficacious dose and safe delivery of docetaxel in combination with darolutamide in ARASENS: A phase III study

Background We assessed the impact of granulocyte colony-stimulating factor (G-CSF) use and docetaxel relative dose intensity (RDI) on the safety profile of the ARASENS (NCT02799602) triplet regimen with darolutamide in patients with metastatic hormone-sensitive prostate cancer. Methods Patients were randomized to darolutamide 600 mg orally twice daily or placebo, with androgen deprivation therapy (ADT) and docetaxel. Baseline characteristics, G-CSF use, and safety were analyzed according to docetaxel RDI (≤85% vs >85%). Results Of 1273 patients with docetaxel RDI data (darolutamide n = 637; placebo n = 636), >97% received an efficacious dose of docetaxel (RDI >80%). Patient demographics and baseline disease characteristics were generally similar between RDI subgroups; >60% of patients with RDI ≤85% were from the Asia-Pacific region. Concomitant G-CSF, with/without docetaxel dose modification, was used in 42.4% (darolutamide) and 44.6% (placebo) of patients, mainly as secondary prophylaxis; 61.3% (darolutamide) and 64.4% (placebo) received both docetaxel dose modifications and G-CSF. Grade ≥3 treatment-emergent adverse events (TEAEs), grade ≥3 neutropenia, and grade ≥3 febrile neutropenia were higher with docetaxel RDI ≤85%, but docetaxel discontinuation rates were similar between subgroups (RDI ≤85%: darolutamide 7.2%, placebo 10.8%; RDI >85%: darolutamide 8.1%, placebo 10.5%). TEAEs leading to docetaxel dose modification were more frequent with docetaxel RDI ≤85% (darolutamide 92.8%; placebo 97.3%) versus RDI >85% (darolutamide 26.0%; placebo 25.3%). Conclusion Appropriate docetaxel dose modifications and early G-CSF use allowed almost all patients to receive an efficacious dose of docetaxel in combination with darolutamide and ADT and may prevent neutropenic complications in patients receiving docetaxel. Prior presentation Previously presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, San Francisco, CA.