Early G-CSF Use Supports Maintenance of Docetaxel Dose Intensity in Metastatic Hormone-Sensitive Prostate Cancer
Clinical Summary:
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Design/Population: This post hoc analysis of the phase 3 ARASENS trial evaluated docetaxel dose intensity and granulocyte colony-stimulating factor (G-CSF) use among patients with metastatic hormone-sensitive prostate cancer receiving darolutamide or placebo in combination with androgen deprivation therapy and docetaxel.
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Key Outcomes: More than 97% of patients maintained a relative docetaxel dose intensity >80%. Patients receiving lower dose intensity experienced higher rates of grade ≥3 adverse events, while G-CSF use and dose modifications enabled most patients to continue treatment.
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Clinical Relevance: These findings support early G-CSF use and appropriate docetaxel dose modifications to maintain chemotherapy delivery while reducing the risk of treatment-related complications in metastatic hormone-sensitive prostate cancer.
Results from a post hoc analysis of the phase 3 ARASENS trial demonstrated that most patients with metastatic hormone-sensitive prostate cancer maintained effective docetaxel dose intensity through early granulocyte colony-stimulating factor (G-CSF) use and appropriate dose modifications while receiving darolutamide plus androgen deprivation therapy (ADT).
“The current standard of care for [metastatic hormone-sensitive prostate cancer] includes the use of ADT in combination with [ARPIs], such as darolutamide, with or without docetaxel,” stated Michael Ong, MD, PhD, The Ottawa Hospital Cancer Centre, Ontario, Canada, and coauthors. “To help mitigate the risk of neutropenic complications, [researchers have turned to] G-CSF prophylaxis and/or docetaxel dose modifications… however, the role and frequency of primary versus secondary G-CSF prophylaxis is still debated in clinical practice.”
This post hoc analysis included 1,273 patients with available relative docetaxel dose intensity data who were randomized to receive either darolutamide or placebo in combination with ADT and docetaxel (75 mg/m² for 6 cycles). Safety outcomes were analyzed according to relative docetaxel dose intensity (≤85% or >85%) and G-CSF use.
Overall, 98.3% of patients in the darolutamide arm and 97.6% of those in the placebo arm maintained a relative docetaxel dose intensity >80%. A relative dose intensity >85% was achieved by 89.2% and 88.4% of patients, respectively.
G-CSF was administered to 42.4% of patients receiving darolutamide and 44.6% of those receiving placebo, most commonly as secondary prophylaxis. Among patients with a relative docetaxel dose intensity ≤85%, G-CSF use increased to 69.6% and 74.3%, respectively, compared with 39.4% and 40.6% among patients who maintained higher dose intensity.
Patients with a relative docetaxel dose intensity of ≤85% experienced higher rates of grade ≥3 treatment-emergent adverse events than those who maintained higher dose intensity. Neutropenia and febrile neutropenia were the most frequently reported severe toxicities. Following an episode of febrile neutropenia, G-CSF was initiated in approximately two-thirds of patients in both treatment arms.
Docetaxel discontinuation rates remained low regardless of dose intensity. Among patients receiving ≤85% of the planned dose intensity, discontinuation occurred in 7.2% of patients receiving darolutamide and 10.8% of those receiving placebo. Among patients maintaining more than 85% dose intensity, discontinuation rates were 6.9% and 8.7%, respectively.
“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,” concluded Dr Ong et al.
Source:
Ong M, Suzuki H, Smith M, et al. Use of concomitant G-CSF in maintaining efficacious dose and safe delivery of docetaxel in combination with darolutamide in ARASENS: A phase III study. Eur J Cancer. Published online: March 11, 2026. doi: 10.1016/j.ejca.2026.116264
