G-CSF Supports Effective Docetaxel Delivery in Metastatic Hormone-Sensitive Prostate Cancer

Clinical Summary: 

• Design/Population: This post hoc analysis of the phase 3 ARASENS trial evaluated docetaxel dose intensity and G-CSF use in 1,273 patients with metastatic hormone-sensitive prostate cancer receiving darolutamide, ADT, and docetaxel.
• Key Outcomes: More than 97% of patients maintained effective docetaxel dosing. Lower dose intensity was associated with increased hematologic toxicity, although discontinuation rates were similar across groups.
• Clinical Relevance: Findings support proactive G-CSF use and dose management strategies to maintain chemotherapy delivery and reduce complications in metastatic hormone-sensitive prostate cancer. 

According to post hoc analysis results from the phase 3 ARASENS trial, early granulocyte colony-stimulating factor (G-CSF) use and appropriate dose modifications allow most patients with metastatic hormone-sensitive prostate cancer to maintain effective docetaxel dosing with manageable toxicity. 

“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.”

Researchers collected data from 1,273 patients with available relative dose intensity data who were randomized 1:1 to receive either 600 mg of twice daily darolutamide or matched placebo plus standard ADT and docetaxel (75 mg/m² for 6 cycles). Safety outcomes were assessed according to docetaxel relative dose intensity (≤ 85% or >85%), as well as G-CSF use. 

At analysis, 98.3% of patients in the darolutamide arm and 97.6% of patients in the placebo arm maintained a relative docetaxel dose intensity >80%. A relative docetaxel dose intensity >85% occurred in 89.2% of patients and 88.4% of patients, respectively. A relative docetaxel dose intensity ≤ 85% occurred in 10.8% of patients in the darolutamide arm and 11.6% of patients in the placebo arm. 

G-CSF was administered in 42.4% of patients in the darolutamide arm and 44.6% of patients in the placebo arm, primarily as secondary prophylaxis. G-CSF use and docetaxel dose modifications were reported in 60.9% of patients in the darolutamide arm and 64.2% of patients in the placebo arm. Among patients with a relative docetaxel dose intensity ≤ 85% G-CSF was administered in 69.6% of patients in the darolutamide arm and 74.3% of patients in the placebo arm. Among patients with a relative docetaxel dose intensity >85%, G-CSF was administered in 39.4% and 40.6% of patients, respectively. 

Grade ≥3 treatment-emergent adverse events were reported in 94.2% of patients in the darolutamide arm and 89.2% of patients in the placebo arm among patients with a relative docetaxel dose intensity ≤85%. Grade ≥3 treatment-emergent adverse events were reported in 66.9% of patients in the darolutamide arm and 65.1% of patients in the placebo arm among patients with a relative docetaxel dose intensity >85%. The most frequently reported treatment-emergent adverse events included neutropenia and febrile neutropenia. Among patients who developed febrile neutropenia, G-CSF was initiated after the first incidence in 64.7% of patients in the darolutamide arm and 61.7% of patients in the placebo arm. 

Among patients with a relative docetaxel dose intensity ≤85%, docetaxel discontinuations occurred in 7.2% of patients in the darolutamide arm and 10.8% of patients in the placebo arm. Among patients with a relative docetaxel dose intensity >85%, docetaxel discontinuations occurred in 6.9% and 8.7% of patients, respectively. 

When patients underwent G-CSF and docetaxel dose modifications, treatment discontinuation rates were 11.7% in the darolutmaide arm and 20.1% in the placebo arm. 

“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