Efbemalenograstim Alfa, a Long-Acting Granulocyte Colony-Stimulating Factor Fusion Protein Without PEGylation, Versus Pegfilgrastim for Management of Chemotherapy-Induced Neutropenia in Patients With Breast Cancer: Results of a Phase III Randomized N

PURPOSE This phase III noninferiority (NI) trial evaluated the efficacy and safety of efbemalenograstim alfa, a novel non-PEGylated, long-acting, human granulocyte-colony stimulating factor for the management of chemotherapy-induced neutropenia (CIN), in patients with breast cancer. MATERIALS AND METHODS Adult patients with stage I-III invasive breast cancer (n = 393) undergoing docetaxel and cyclophosphamide chemotherapy treatment were randomly assigned (1:1) to receive a single fixed dose of efbemalenograstim alfa or pegfilgrastim 24 hours after each chemotherapy administration. The primary objective was to demonstrate NI or potential superiority of efbemalenograstim alfa compared with pegfilgrastim. The primary end point is the duration of severe neutropenia (DSN) in cycle 1 with a NI margin of 0.6 days. Additional end points included incidence of severe neutropenia (ISN), febrile neutropenia, infections, and incidence of treatment-emergent adverse events (TEAEs). RESULTS Among patients randomly assigned to efbemalenograstim alfa (n = 197), the mean DSN in cycle one was 0.2 ± 0.51 days, compared with 0.2 ± 0.45 days for the pegfilgrastim group (n = 196), with a CI of –0.1 to 0.1 days ( P = .7) for the treatment comparison, confirming NI. There was a lower ISN in those receiving efbemalenograstim alfa at cycle 4 ( P = .050). Lower ISN in later cycles was observed in all three efbemalenograstim alfa phase III trials. Treatment with efbemalenograstim alfa was safe, with low incidences of serious AEs and TEAEs, and an overall safety profile comparable with the pegfilgrastim group. Similar to ISN, fewer grade 4 neutropenias in the efbemalenograstim alfa group were observed compared with pegfilgrastim. CONCLUSION Results demonstrated that efbemalenograstim alfa was noninferior to current CIN therapy (pegfilgrastim) with comparable efficacy and safety profiles in cycle 1 and showed evidence of less neutropenia in later cycles.