title: A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients.
abstract: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator.
  This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade.
  The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety.
  The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯).
authors.affiliation: Hospital Pérola Byington, Centro de Referência da Saúde da Mulher, São Paulo/SP, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Hegg
authors.affiliation: Hospital Pérola Byington, Centro de Referência da Saúde da Mulher, São Paulo/SP, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Mattar
authors.affiliation: Hospital Universitário de Brasília, Brasília/DF, Brazil.
authors.forename: João Nunes de
authors.initials: JN
authors.lastname: Matos-Neto
authors.affiliation: Hospital Nossa Senhora da Conceição, Porto Alegre/RS, Brazil.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Pedrini
authors.affiliation: Hospital Evangélico de Cachoeiro de Itapemirim, Cachoeiro de Itapemirim/ES, Brazil.
authors.forename: Sabina Bandeira
authors.initials: SB
authors.lastname: Aleixo
authors.affiliation: Hospital Santa Marcelina, São Paulo/SP, Brazil.
authors.forename: Roberto Odebrecht
authors.initials: RO
authors.lastname: Rocha
authors.affiliation: Hospital Bruno Born, Lajeado/RS, Brazil.
authors.forename: Renato Peixoto
authors.initials: RP
authors.lastname: Cramer-Junior
authors.affiliation: Instituto do Câncer Arnaldo Vieira de Carvalho, São Paulo/SP, Brazil.
authors.forename: Sylvie
authors.initials: S
authors.lastname: van-Eyll-Rocha
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects; D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D000069585:Filgrastim / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006401:Hematologic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000517:prevention & control*; D012016:Reference Values; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D059451:Biosimilar Pharmaceuticals; D006401:Hematologic Agents; D000069585:Filgrastim