Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial.

PURPOSE: Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012-07-19). METHODS: 232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle. RESULTS: Efbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7-8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 109/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 109/L after the expected ANC nadir) was 2.0-2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 109/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug. CONCLUSION: Efbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety. GOV IDENTIFIER: NCT01648322.

Efbemalenograstim alfa, an Fc fusion protein, long-acting granulocyte-colony stimulating factor for reducing the risk of febrile neutropenia following chemotherapy: results of a phase III trial.

PURPOSE: Evaluate the safety and efficacy of efbemalenograstim alfa for reducing the risk of febrile neutropenia in breast cancer patients undergoing myelosuppressive chemotherapy. METHODS: A phase III, randomized, double-blind, placebo-controlled study was conducted. A total of 122 subjects received up to 4 cycles of TA chemotherapy (75 mg/m2 docetaxel + 60 mg/m2 doxorubicin). Patients were randomized in a 2:1 ratio to subcutaneously inject a single 20 mg of efbemalenograstim alfa or placebo on day 2 of cycle 1, and all subjects received efbemalenograstim alfa on day 2 of cycles 2, 3, and 4. Duration of severe (grade 4) neutropenia (DSN), depth of neutrophil nadir, incidence of febrile neutropenia (FN), time to neutrophil recovery, and safety information were recorded. RESULTS: For the primary endpoint, the mean DSN in cycle 1 was 1.3 days and 3.9 days for efbemalenograstim alfa and placebo respectively (95% CI, 2.3, 3.4). As the lower bound of the 95% CI was > 0, superiority of efbemalenograstim alfa over placebo can be declared. In addition, the incidence of FN in Cycle 1 was lower in efbemalenograstim alfa group than in placebo group (4.8% vs. 25.6%; p = 0.0016). Patients in the efbemalenograstim alfa group required less intravenous antibiotics (3.6% vs. 17.9%; p = 0.0119). Most adverse events were consistent with those expected for breast cancer patient receiving TA chemotherapy. CONCLUSION: Efbemalenograstim alfa is effective and safe for significantly decreasing the duration of severe neutropenia and the incidence of febrile neutropenia in breast cancer patients who are receiving TA chemotherapy. TRIAL REGISTRATION: NCT02872103, August 19, 2016.