The effect of filgrastim or pegfilgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy

摘要

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. Patients and 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 logrank 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.