title: Phase III, randomized, double-blind, placebo-controlled, multicenter study of lipegfilgrastim in patients with non-small cell lung cancer receiving myelosuppressive therapy.
abstract: OBJECTIVE
  The aim of this study was to demonstrate lipegfilgrastim superiority versus placebo in adults with non-small cell lung cancer receiving myelosuppressive chemotherapy.
  
  
  METHODS
  This 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).
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Lipegfilgrastim 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.
authors.affiliation: Centrul de Oncologie Medicala, Vasile Conta 2 Str, 700106 Iasi, Romania.
authors.forename: Constantin
authors.initials: C
authors.lastname: Volovat
authors.affiliation: Dnipropetrovsk State Medical Academy, City Clinical Hospital, N 4, 31, Glizhnaya Str, Dnipropetrovsk, 49102 Ukraine.
authors.forename: Igor M
authors.initials: IM
authors.lastname: Bondarenko
authors.affiliation: Chelyabinsk Regional Clinical Oncology Dispensary, 42, Blukhera Str., Chelyabinsk, 454087 Russia.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Gladkov
authors.affiliation: Teva Ratiopharm, Merckle GmbH, Graf-Arco-Strasse 3, 89079 Ulm, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Elsässer
authors.affiliation: Teva Ratiopharm, Merckle GmbH, Graf-Arco-Strasse 3, 89079 Ulm, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Buchner
authors.affiliation: Teva Ratiopharm, Merckle GmbH, Graf-Arco-Strasse 3, 89079 Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bias
authors.affiliation: Teva Pharmaceuticals, Inc., Graf-Arco-Strasse 3, 89079 Ulm, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Müller
keywords: Lipegfilgrastim; Neutropenia; Non-small cell lung cancer; Phase III clinical trial; Recombinant granulocyte colony-stimulating factor