Phase III, randomized, double-blind, placebo-controlled, multicenter study of lipegfilgrastim in patients with non-small cell lung cancer receiving myelosuppressive therapy.

Constantin Volovat,Peter Bias,Oleg A Gladkov,Reiner Elsässer,Igor M Bondarenko,Anton Buchner,Udo Müller

doi:10.1186/s40064-015-1067-7

Abstract

PurposeThe aim of this study was to demonstrate lipegfilgrastim superiority versus placebo in adults with non-small cell lung cancer receiving myelosuppressive chemotherapy.MethodsThis phase III, double-blind study randomized chemotherapy-naive patients to receive cisplatin and etoposide with either lipegfilgrastim 6 mg or placebo. Because of the placebo control, patients at individual high risk for febrile neutropenia (FN; ≥20%) were excluded. Study drug was administered on day 4 (24 h after chemotherapy) of a 21-day cycle for ≤4 cycles. Primary efficacy measure was FN incidence in cycle 1. Secondary assessments included duration of severe neutropenia (DSN), absolute neutrophil count (ANC) profile, and adverse events (AEs).ResultsThe study included 375 patients (lipegfilgrastim, n = 250; placebo, n = 125). Lipegfilgrastim superiority for FN incidence in cycle 1 was not achieved but incidence was lower (2.4%) versus placebo (5.6%). Cycle 1 mean DSN was significantly shorter for lipegfilgrastim (0.6 ± 1.1 days) versus placebo (2.3 ± 0.5 days; p < 0.0001). Incidence of severe neutropenia was significantly lower for lipegfilgrastim versus placebo overall and in each cycle (all, p < 0.0001). Mean ANC nadir was lowest in cycle 1 but significantly higher for lipegfilgrastim (1.60 ± 1.64) than placebo (0.67 ± 0.85; p < 0.0001). Mean time to ANC recovery was shorter with lipegfilgrastim in each cycle. Treatment-emergent AEs were similar between treatment groups.ConclusionsLipegfilgrastim was not statistically superior to placebo for incidence of FN in cycle 1, but was more effective in reducing incidence of severe neutropenia, DSN, and time to ANC recovery, with an acceptable safety profile.Controlled-trials.com identifier: ISRCTN55761467.

Highlights

Neutropenia is a major dose-limiting toxicity in many myelosuppressive chemotherapy regimens (Holmes et al 2002; Crawford et al 2013)
Volovat et al SpringerPlus (2015) 4:316 and are recommended in European and US guidelines for chemotherapy patients at high (≥20%) risk of febrile neutropenia (FN) (Crawford et al 2010, 2013; Smith et al 2006; Aapro et al 2011)
It is approved by the European Medicines Agency for reducing the duration of neutropenia and the incidence of FN in adults treated with cytotoxic chemotherapy for malignancy (Lonquex 2013)

Summary

Introduction

Neutropenia is a major dose-limiting toxicity in many myelosuppressive chemotherapy regimens (Holmes et al 2002; Crawford et al 2013). A patient’s risk of developing neutropenia or febrile neutropenia (FN) depends on Recombinant granulocyte colony-stimulating factors (G-CSFs) promote the proliferation and differentiation of neutrophils, alleviating the severity of chemotherapyinduced neutropenia and FN (Cooper et al 2011). These agents are well established as primary prophylaxis for FN. Lipegfilgrastim is a glycoPEGylated, once-per-cycle recombinant human G-CSF expressed in Escherichia coli It is approved by the European Medicines Agency for reducing the duration of neutropenia and the incidence of FN in adults treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes) (Lonquex 2013)

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