title: Comparison of effectiveness of biosimilar filgrastim (Nivestim™), reference Amgen filgrastim and pegfilgrastim in febrile neutropenia primary prevention in breast cancer patients treated with neo(adjuvant) TAC: a non-interventional cohort study.
abstract: OBJECTIVE
  Biosimilars are supported by limited clinical data at the time of approval. Recently, Nivestim™, a biosimilar of reference of filgrastim, was approved for prevention of chemotherapy-related febrile neutropenia (FN). To add clinical experience to this new biosimilar, we performed a study to compare the effectiveness of Nivestim™ with reference filgrastim and pegfilgrastim in FN prevention in patients receiving high-risk FN chemotherapy.
  
  
  METHODS
  This is a comparative cohort study, with retrospective data collection. Three cohorts were identified according to the type of primary prophylaxis employed over different time periods: reference filgrastim (2004-2006), pegfilgrastim (2007-2008) and biosimilar filgrastim (2011-2012). The study included female patients with early breast cancer that received FN primary prophylaxis during (neo)adjuvant docetaxel/doxorubicin/cyclophosphamide (TAC).
  
  
  RESULTS
  Reference filgrastim cohort included 147 patients and pegfilgrastim and biosimilar filgrastim cohorts 139 and 134 patients, respectively. FN rates per patient/cycle were 16 % (95 % confidence interval (CI) 10.2-22.5 %)/3 % (95 % CI 2.1-4.7 %) in the reference filgrastim group, 9 % (95 % CI 4.5-14.6 %)/2 % (95 % CI 1.3-3.6 %) in the pegfilgrastim group and 16 % (95 % CI 10.0-22.9 %)/4 % (95 % CI 2.5-5.3 %) in the biosimilar filgrastim cohort. The median absolute neutrophil count (ANC) at FN presentation was lower in the biosimilar group in comparison with reference filgrastim. FN episodes with ANC < 100 cells/μL were more frequent in the biosimilar group (50 %) when compared with reference filgrastim (4 %) and pegfilgrastim (6 %). No differences concerning FN complications were seen, with the exception of more chemotherapy delays in the biosimilar group when compared with pegfilgrastim.
  
  
  CONCLUSIONS
  No differences in biosimilar effectiveness were detected. The clinical relevance of the profound neutropenia found in the biosimilar cohort needs further attention.
authors.affiliation: Medical Oncology Department, Instituto Português de Oncologia Francisco Gentil, Rua Prof. Lima Basto, 1099-023, Lisbon, Portugal. margarida.brito@gmail.com.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-6104-5902
authors.initials: M
authors.lastname: Brito
authors.affiliation: Clinical Research Unit, Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Esteves
authors.affiliation: Medical Oncology Department, Instituto Português de Oncologia Francisco Gentil, Rua Prof. Lima Basto, 1099-023, Lisbon, Portugal.|Oncology Department, Novartis Farma SA, Lisbon, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: André
authors.affiliation: Pharmacy Department, Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Isidoro
authors.affiliation: Medical Oncology Department, Instituto Português de Oncologia Francisco Gentil, Rua Prof. Lima Basto, 1099-023, Lisbon, Portugal.|Clinical Research Unit, Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Moreira
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D000069585:Filgrastim / Q000008:administration & dosage*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D059451:Biosimilar Pharmaceuticals; D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069585:Filgrastim
keywords: Breast cancer; Febrile neutropenia; Filgrastim; G-CSF biosimilar