Justification for a Fixed Dose of Eflapegrastim, a Long‐Acting G‐CSF, in Patients Receiving Docetaxel‐Cyclophosphamide Chemotherapy

Abstract Eflapegrastim (Rolontis) is a long‐acting granulocyte colony‐stimulating factor (G‐CSF) produced by conjugating a human G‐CSF analogue and a human immunoglobulin G4 Fc fragment, linked via a polyethylene glycol linker. Weight‐based doses of 45 to 270 μg/kg eflapegrastim (12.3‐73.6 μg/kg as G‐CSF) were evaluated in a phase 2 study in patients. Based on these results, a fixed dose of 13.2 mg eflapegrastim (3.6 mg G‐CSF) was compared with pegfilgrastim (6 mg G‐CSF) in 2 phase 3 studies and in a pharmacokinetic single‐arm multicenter study. Absolute neutrophil count (ANC) data from these 3 studies were evaluated in patients with early‐stage breast cancer who were treated with docetaxel and cyclophosphamide (n = 669). Serum concentrations of eflapegrastim were determined by enzyme‐linked immunosorbent assay. Eflapegrastim systemic exposures were higher in cycle 1 than in cycle 3, likely attributable to the higher ANC in cycle 3, increasing neutrophil‐mediated clearance. Eflapegrastim elicited a greater effect on ANC than pegfilgrastim in patients at ∼60% of the G‐CSF dose. Body weight had no clinically significant effect on response, justifying administration of a fixed dose of eflapegrastim. The results from 2 phase 3 studies demonstrate that eflapegrastim at a fixed dose of 13.2 mg (3.6 mg G‐CSF) administered once per chemotherapy cycle is effective in prophylactic treatment of chemotherapy‐induced neutropenia.