Background and ObjectivesNeutropenia is the most severe hematologic toxicity of myelosuppressive chemotherapy. The objective of this study was to evaluate the safety and efficacy of efbemalenograstim alfa versus filgrastim for neutropenia support in patients with breast cancer receiving myelosuppressive chemotherapy and find the recommended dose for phase III clinical trials.MethodsThis was an open-label, dose-finding, active-controlled, phase II study. In total, 138 patients with postoperative breast cancer received up to four cycles of epirubicin 100 mg/m2 + cyclophosphamide 600 mg/m2 (EC) chemotherapy. Patients were randomized in a 1:1:1 ratio to efbemalenograstim alfa (10 mg/dose or 20 mg/dose) or filgrastim group. Duration and incidence rate of moderate or severe neutropenia, depth of absolute neutrophil count (ANC) nadir, time to ANC recovery post nadir, and safety information were evaluated.ResultsThe mean duration of moderate and severe neutropenia in cycle 1 was 0.8, 0.6, and 0.8 days for the 10 mg/dose efbemalenograstim alfa, 20 mg/dose efbemalenograstim alfa, and filgrastim groups, respectively. The incidence rate of moderate and severe neutropenia in cycle 1 was lower in 20 mg/dose efbemalenograstim alfa (25.5%) than that in 10 mg/dose efbemalenograstim alfa (35.1%) and filgrastim (38.5%), and no significant differences were observed for the two doses of efbemalenograstim alfa with filgrastim (p = 0.815; p = 0.246, respectively). The ANC nadir occurred between days 9 and 10 in cycle 1, and the median ANC nadir in the 20 mg/dose efbemalenograstim alfa group was higher than that in the 10 mg/dose efbemalenograstim alfa and filgrastim groups (2.2 x 109/L versus 1.7 x 109/L and 1.4 x 109/L, respectively). The time to ANC recovery post nadir in the 20 mg/dose efbemalenograstim alfa group was shorter, but no significant differences were observed for the two doses of efbemalenograstim alfa with filgrastim (0.8 and 1.7 versus 1.2 days, respectively). Efbemalenograstim alfa exhibited similar safety profile to filgrastim. No febrile neutropenia occurred. The incidence rates of common adverse reactions related to the study drugs, such as back pain and bone pain, were lower in the efbemalenograstim alfa groups than that in the filgrastim group (10.3% and 8.0% versus 24.4%).ConclusionsThe efficacy and safety of efbemalenograstim alfa are comparable to those of filgrastim in treating chemotherapy-induced neutropenia in patients with breast cancer receiving EC chemotherapy. Efbemalenograstim alfa at a dose of 20 mg is the recommended dose for phase III clinical trials.Trial RegistrationClinicalTrials.gov: NCT02521441, on 13 August 2015.