A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer

Ann Oncol. 2020 Jul;31(7):951-957. doi: 10.1016/j.annonc.2020.04.005. Epub 2020 Apr 20.


Background: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days.

Patients and methods: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy.

Results: Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%).

Conclusion: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS.

Gov registration: NCT02428114 and NCT02816164.

Keywords: breast cancer; filgrastim; supportive care.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms* / drug therapy
  • Chemotherapy-Induced Febrile Neutropenia* / epidemiology
  • Chemotherapy-Induced Febrile Neutropenia* / etiology
  • Chemotherapy-Induced Febrile Neutropenia* / prevention & control
  • Febrile Neutropenia* / chemically induced
  • Febrile Neutropenia* / epidemiology
  • Febrile Neutropenia* / prevention & control
  • Filgrastim / therapeutic use
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins / therapeutic use


  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Polyethylene Glycols
  • Filgrastim

Associated data

  • ClinicalTrials.gov/NCT02428114
  • ClinicalTrials.gov/NCT02816164

Grants and funding