title: Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy.
abstract: BACKGROUND
  Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen(®), in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC).
  
  
  METHODS
  A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomized 1:1:1:1 into four arms. Two arms received only one product (nonalternating), biosimilar or reference, and two arms (alternating) received alternating treatments during each cycle (biosimilar then reference or vice versa). The primary end point was duration of severe neutropenia (DSN) during cycle 1.
  
  
  RESULTS
  The baseline characteristics were balanced between the four treatment arms. Noninferiority of biosimilar versus the reference was demonstrated: DSN (days) in cycle 1 was 1.17 ± 1.11 (biosimilar, N = 101) and 1.20 ± 1.02 (reference, N = 103), 97.5% confidence interval lower boundary for the difference was -0.26 days (above the predefined limit of -1 day). No clinically meaningful differences were observed regarding any other efficacy parameter: incidence of febrile neutropenia (FN); hospitalization due to FN; incidence of infections; depth and time of absolute neutrophil count (ANC) nadir and time to ANC recovery during cycle 1 and across all cycles. The pattern and frequency of adverse events were similar across all treatments.
  
  
  CONCLUSIONS
  This study demonstrates that biosimilar and the reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially benefiting public health by increasing access to filgrastim treatment.
  NCT01519700.
authors.affiliation: Duke University, DUMC, Durham, USA. Electronic address: kimberly.blackwell@duke.edu.
authors.forename: K
authors.initials: K
authors.lastname: Blackwell
authors.affiliation: 'Railway Clinical Hospital of OJSC "RZhD"', Non-State Healthcare Institution (NSHI), Saint Petersburg.
authors.forename: V
authors.initials: V
authors.lastname: Semiglazov
authors.affiliation: 'Leningrad Regional Oncological Dispensary' at the Surgery Department #2, State Healthcare Institution (SHI), Saint Petersburg.
authors.forename: D
authors.initials: D
authors.lastname: Krasnozhon
authors.affiliation: 'Clinical Oncological Dispensary No. 1' of Healthcare Department of Krasnodar Territory, State Healthcare Institution (SHI), Krasnodar.
authors.forename: I
authors.initials: I
authors.lastname: Davidenko
authors.affiliation: Institution of the Russian Academy of Medical Sciences, 'Russian Oncology Research Center n.a. N.N. Blochin of RAMS', Moscow, Russia.
authors.forename: L
authors.initials: L
authors.lastname: Nelyubina
authors.affiliation: Hexal AG, Holzkirchen.
authors.forename: R
authors.initials: R
authors.lastname: Nakov
authors.affiliation: Hexal AG, Holzkirchen.
authors.forename: G
authors.initials: G
authors.lastname: Stiegler
authors.affiliation: Hexal AG, Holzkirchen.
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.affiliation: Hexal AG, Holzkirchen.
authors.forename: A
authors.initials: A
authors.lastname: Schwebig
authors.affiliation: Hexal AG, Holzkirchen.
authors.forename: S
authors.initials: S
authors.lastname: Kramer
authors.affiliation: Breast Center, University of Munich, Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Harbeck
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D000069585:Filgrastim / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009503:Neutropenia / Q000188:drug therapy / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D059451:Biosimilar Pharmaceuticals; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim
keywords: biosimilars; filgrastim; granulocyte colony-stimulating factor; neutropenia