Abstract
Lipegfilgrastim is a long-acting, once-per-cycle, glycopegylated recombinant granulocyte colony-stimulating factor (G-CSF) used to prevent neutropenia in patients receiving myelosuppressive chemotherapy. This integrated analysis examined the immunogenicity of lipegfilgrastim and its potential clinical impact in two double-blind randomized studies (phases II and III) of patients with breast cancer receiving chemotherapy. Serum samples were analyzed using sequential assays for screening, confirmation, antibody titer, and characterization of antidrug antibodies (ADA). Neutropenia-related efficacy measures were reviewed for each ADA-positive patient. Among 255 patients receiving lipegfilgrastim (154 in phase II, 101 in phase III) and 155 patients receiving pegfilgrastim (54 in phase II, 101 in phase III), the incidence of treatment-emergent ADA was low and similar between the lipegfilgrastim (phase II: 1.3%; phase III: 1.0%) and pegfilgrastim (phase II: 1.9%; phase III: 1.0%) arms. None of the treatment-emergent ADA-positive samples exhibited neutralizing activity against lipegfilgrastim, pegfilgrastim, or glycosylated G-CSF in a cell-based neutralizing antibody assay. No changes were observed in neutropenia-related efficacy measures among ADA-positive patients, and no treatment-related hypersensitivity or anaphylaxis occurred. These results indicate that there is no apparent impact of ADA on lipegfilgrastim efficacy and safety.
Highlights
Granulocyte colony-stimulating factor (G-CSF) is an endogenous growth factor that promotes neutrophil production, maturation, survival, and activity [1]
These results indicate that there is no apparent impact of antidrug antibodies (ADA) on lipegfilgrastim efficacy and safety
The CD34+ values for these two patients were similar to those from ADA-negative subjects. The objective of this analysis was to assess the immunogenicity of lipegfilgrastim in patients receiving chemotherapy for breast cancer
Summary
Granulocyte colony-stimulating factor (G-CSF) is an endogenous growth factor that promotes neutrophil production, maturation, survival, and activity [1]. Recombinant G-CSFs, such as filgrastim and pegfilgrastim, are used commonly for the prevention and treatment of neutropenia in patients receiving myelosuppressive chemotherapy [2,3,4]. Conjugating filgrastim to polyethylene glycol (PEG; pegylation yielding pegfilgrastim) reduces renal clearance and extends the drug’s half-life such that it need be administered only once per chemotherapy treatment cycle, with efficacy and safety comparable to those of daily filgrastim [5,6,7]. The noninferiority of lipegfilgrastim to pegfilgrastim in the treatment of severe neutropenia was demonstrated in a randomized, double-blind, active-controlled, phase III trial evaluating the efficacy and safety of lipegfilgrastim in 202 chemotherapy naive patients with breast cancer [9]. Lipegfilgrastim was approved in the European Union in 2013 as onceper-cycle, fixed-dose prophylaxis for severe neutropenia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
