title: The effect of filgrastim or pegfilgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy.
abstract: BACKGROUND
  Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is associated with higher chemotherapy relative dose intensity, which may lead to improved outcomes; however, the association between G-CSF primary prophylaxis and overall survival (OS) is not well characterized. This study assessed the effect of G-CSF primary prophylaxis on patient outcomes in randomized, controlled, registrational clinical trials of filgrastim and pegfilgrastim.
  
  
  METHODS
  Three placebo-controlled and two non-inferiority clinical trials of filgrastim and/or pegfilgrastim in patients receiving myelosuppressive chemotherapy for lung, breast, or colorectal cancer were included. The median OS, 6- and 12-month survival rates, and hazard ratios [HRs; unadjusted Cox model with 95% confidence intervals (CIs)] were estimated for patients receiving ≥1 dose of filgrastim, pegfilgrastim, or placebo. Comparisons were based on a log-rank test. A fixed-effect meta-analysis assessed the effect of primary prophylaxis with filgrastim/pegfilgrastim on OS in the placebo-controlled trials.
  
  
  RESULTS
  In patients with lung cancer receiving filgrastim versus placebo, the median OS was 14.1 versus 11.1 months (HR, 0.81; 95% CI 0.48-1.35; P = 0.412); in patients who crossed over to filgrastim from placebo after cycle 1, the median OS was 16.9 months (HR, 0.75; 95% CI 0.43-1.28; P = 0.286). The median OS was inestimable in at least one treatment arm in the other studies because of the small number of OS events. Where estimable, 6- and 12-month survival rates were generally greater among patients receiving filgrastim/pegfilgrastim versus placebo. In the meta-analysis of placebo-controlled studies comparing G-CSF primary prophylaxis with placebo in the as-treated analysis sets, the HR (95% CI) for OS was 0.77 (0.58-1.03).
  
  
  CONCLUSIONS
  In this retrospective analysis, OS point estimates were greater among patients receiving filgrastim versus placebo, but the differences were not statistically significant. Further studies evaluating patient outcomes with G-CSF prophylaxis are warranted.
  
  
  BACKGROUND
  NCT00035594, NCT00094809.
authors: Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center and the Department of Medicine, University of Washington, Seattle glyman@fredhutch.org.
authors: G H
authors: GH
authors: Lyman
authors: Global Biostatistical Science, Amgen Inc., Thousand Oaks.
authors: M
authors: M
authors: Reiner
authors: Hematology/Oncology, Amgen Inc., Thousand Oaks.
authors: P K
authors: PK
authors: Morrow
authors: Department of Medicine, Duke University School of Medicine, and Duke Cancer Institute, Durham, USA.
authors: J
authors: J
authors: Crawford
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D000069585:Filgrastim / Q000627:therapeutic use*; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006401:Hematologic Agents / Q000627:therapeutic use; D006760:Hospitalization; D006801:Humans; D015201:Meta-Analysis as Topic; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D011092:Polyethylene Glycols; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D006401:Hematologic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim
keywords: G-CSF; filgrastim; neutropenia; overall survival; pegfilgrastim