A Phase III Study of Balugrastim Versus Pegfilgrastim in Breast Cancer Patients Receiving Chemotherapy With Doxorubicin and Docetaxel

Oncologist. 2016 Jan;21(1):7-15. doi: 10.1634/theoncologist.2015-0152. Epub 2015 Dec 14.

Abstract

Objectives: This study aimed to evaluate the efficacy and safety of once-per-cycle balugrastim versus pegfilgrastim for neutrophil support in breast cancer patients receiving myelosuppressive chemotherapy.

Methods: Breast cancer patients (n = 256) were randomized to 40 or 50 mg of subcutaneous balugrastim or 6 mg of pegfilgrastim ≈24 hours after chemotherapy (60 mg/m(2) doxorubicin and 75 mg/m(2) docetaxel, every 21 days for up to 4 cycles). The primary efficacy parameter was the duration of severe neutropenia (DSN) in cycle 1. Secondary parameters included DSN (cycles 2-4), absolute neutrophil count (ANC) nadir, febrile neutropenia rates, and time to ANC recovery (cycles 1-4). Safety, pharmacokinetics, and immunogenicity were assessed.

Results: Mean cycle 1 DSN was 1.0 day with 40 mg of balugrastim, 1.3 with 50 mg of balugrastim, and 1.2 with pegfilgrastim (upper limit of 95% confidence intervals for between-group DSN differences was <1.0 day for both balugrastim doses versus pegfilgrastim). Between-group efficacy parameters were comparable except for time to ANC recovery in cycle 1 (40 mg of balugrastim, 2.0 days; 50 mg of balugrastim, 2.1; pegfilgrastim, 2.6). Median terminal elimination half-life was ≈37 hours for 40 mg of balugrastim, ≈36 for 50 mg of balugrastim, and ≈45 for pegfilgrastim. Antibody response to balugrastim was low and transient, with no neutralizing effect.

Conclusion: Once-per-cycle balugrastim is not inferior to pegfilgrastim in reducing cycle 1 DSN in breast cancer patients receiving chemotherapy; both drugs have comparable safety profiles.

Implications for practice: This paper provides efficacy and safety data for a new, once-per-cycle granulocyte colony-stimulating factor, balugrastim, for the prevention of chemotherapy-induced neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. In this phase III trial, balugrastim was shown to be not inferior to pegfilgrastim in the duration of severe neutropenia in cycle 1 of doxorubicin/docetaxel chemotherapy, and the safety profiles of the two agents were similar. Once-per-cycle balugrastim is a safe and effective alternative to pegfilgrastim for hematopoietic support in patients with breast cancer receiving myelosuppressive chemotherapy associated with a greater than 20% risk of developing febrile neutropenia.

Keywords: Balugrastim; Breast cancer; Granulocyte colony-stimulating factor; Myelosuppressive therapy; Pegfilgrastim.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Blood Cell Count
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug-Related Side Effects and Adverse Reactions / drug therapy
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Humans
  • Middle Aged
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Polyethylene Glycols
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Serum Albumin / administration & dosage*
  • Serum Albumin / adverse effects
  • Serum Albumin, Human
  • Taxoids / administration & dosage
  • Taxoids / adverse effects

Substances

  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Serum Albumin
  • Taxoids
  • Granulocyte Colony-Stimulating Factor
  • Docetaxel
  • pegfilgrastim
  • Polyethylene Glycols
  • Doxorubicin
  • Filgrastim
  • balugrastim
  • Serum Albumin, Human