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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., (©AlphaMed Press.)

Balugrastim is a once-per-cycle, fixed-dose recombinant protein comprising human serum albumin and granulocyte colony-stimulating factor under development for prevention of severe neutropenia in cancer patients receiving myelosuppressive chemotherapy. This phase II, multicenter, active-controlled, dose-finding pilot study evaluated balugrastim safety and efficacy versus pegfilgrastim in breast cancer patients scheduled to receive myelosuppressive chemotherapy and investigated two doses with similar efficacy to pegfilgrastim for a subsequent phase III study. Patients received four cycles of doxorubicin/docetaxel chemotherapy and with each successive cycle were randomized sequentially to escalating doses of balugrastim [30 (n = 11), 40 (n = 21), or 50 mg (n = 20)] or a fixed dose of pegfilgrastim [6 mg (n = 26)] post-chemotherapy. Balugrastim doses were escalated as planned. The incidence of adverse events was similar among the balugrastim groups and between all balugrastim doses and pegfilgrastim. The most frequently reported adverse events were neutropenia, alopecia, and nausea. During cycle 1, severe neutropenia (absolute neutrophil count of <0.5 × 10(9)/L) occurred in 40, 67, and 50 % and febrile neutropenia occurred in 20.0, 9.5, and 10.0 % of patients receiving balugrastim 30, 40, and 50 mg, respectively; in patients receiving pegfilgrastim, 48 % experienced severe neutropenia and 8 % experienced febrile neutropenia. Duration of severe neutropenia (DSN) for each treatment group was 0.9, 1.6, 1.1, and 0.9 days, respectively. In the remaining three chemotherapy cycles, DSN was ≤1 day across all treatment groups. Balugrastim 50 mg was comparable to pegfilgrastim in terms of safety and overall efficacy in breast cancer patients receiving myelosuppressive chemotherapy.

Purpose: To evaluate safety of balugrastim, a recombinant human serum albumin and granulocyte colony-stimulating factor (G-CSF), administered over a range of therapeutic doses in women with breast cancer receiving doxorubicin plus docetaxel chemotherapy., Methods: The phase I, sequential dose-escalation first segment compared subcutaneous balugrastim 50, 150, 300, and 450 µg/kg during chemotherapy cycles 0-2. The randomized (2:2:1), open-label, phase IIa second segment compared balugrastim 300 or 450 µg/kg with pegfilgrastim 6 mg during chemotherapy cycles 1 and 2., Results: In the phase I segment, balugrastim was escalated to 450 µg/kg in 13 patients without dose-limiting toxicity. Three (9.7 %) of the 31 adverse events (AEs) reported in nine patients were grade 3 (agranulocytosis, vomiting, hypertension); none was grade 4. In the open-label phase IIa segment (N = 51), the majority of the 64 AEs reported in 31 (75.6 %) balugrastim-treated patients were grade 1 (59.4 %), with 39.1 % grade 2, 1.6 % grade 3 (one AE of vomiting), and none grade 4. Of the 16 AEs reported in seven (70.0 %) pegfilgrastim-treated patients, 87.5 % were grade 1, 6.3 % were grade 2, 6.3 % were grade 3 (one AE of thrombocytopenia), and none were grade 4. Overall, there were six bone pain AEs reported, one in the balugrastim 300 µg/kg group and five in the balugrastim 450 µg/kg group. No AEs in either study necessitated treatment interruption/discontinuation. The incidence and duration of grade 3-4 neutropenia were similar between balugrastim- and pegfilgrastim-treated patients., Conclusions: Balugrastim was well tolerated in this small population of breast cancer patients.

Background: Recombinant granulocyte colony-stimulating factors (G-CSFs) reduce the incidence and duration of chemotherapy-induced neutropenia and febrile neutropenia when given as adjunct therapy to patients receiving myelosuppressive chemotherapy. Balugrastim is a long-acting G-CSF composed of a genetic fusion between recombinant human serum albumin and G-CSF. We compared the efficacy and safety of balugrastim and pegfilgrastim, a long-acting pegylated recombinant G-CSF, in patients with breast cancer who were scheduled to receive chemotherapy., Patients and Methods: In this double-blind randomized phase III trial, patients with ≥ 1.5 × 10(9) neutrophils/L were randomly assigned to subcutaneous injections of balugrastim 40 mg (n = 153) or pegfilgrastim 6 mg (n = 151). The primary efficacy end point was the duration of severe neutropenia (DSN) (days with an absolute neutrophil count [ANC] < 0.5 × 10(9) cells/L) during cycle 1. Efficacy analyses were performed in the per-protocol (PP) population. In a separate open-label single-arm study, newly recruited patients (n = 77) received balugrastim 40 mg and were included in the safety analysis., Results: The mean DSN in cycle 1 was 1.1 days in the balugrastim group and 1.0 days in the pegfilgrastim group (95% confidence interval [CI], -0.13-0.37). Two and 4 patients, respectively, had febrile neutropenia during cycle 1. Twenty percent of patients in the balugrastim group and 19% in the pegfilgrastim group had adverse events (AEs) considered to be related to study medication; 3.9% and 4.7% of patients, respectively, experienced serious AEs., Conclusions: This study demonstrates the comparable safety and efficacy profile of balugrastim and pegfilgrastim and the noninferiority of balugrastim for reduction in DSN. There were no unexpected safety events., (Copyright © 2014 Elsevier Inc. All rights reserved.)