Mitchell S, Li X, Woods M, Garcia J, Hebard-Massey K, Barron R, Samuel M. Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: a systematic review. J Oncol Pharm Pract. 2016 Oct;22(5):702-16. doi: 1078155215625459

Introduction: Febrile neutropenia (FN) is a serious side effect of myelosuppressive chemotherapy. Several clinical trials and observational studies have evaluated the effects of prophylactic granulocyte colony-stimulating factors (G-CSFs) on risk of FN and related complications; however, no systematic reviews have focused on effectiveness in routine clinical practice. Here, we perform a systematic review assessing the comparative effectiveness of prophylaxis with a long-acting G-CSF (pegfilgrastim) versus short-acting G-CSFs (filgrastim, lenograstim, and filgrastim biosimilars) in cancer patients in real-world clinical settings.

Methods: A systematic review was performed based on a pre-specified protocol and was consistent with the Cochrane Collaboration Handbook (2009) and the Centre for Reviews and Dissemination’s Guidance for Undertaking Reviews in Health Care (2011). MEDLINE, Embase, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases were searched for articles published from January 2002 to June 2014. Congress databases (MASCC/ASCO/ESMO) and Google Scholar were searched for abstracts published from January 2012 to August 2014. Filgrastim (NEUPOGEN®), lenograstim, and nivestim (a filgrastim biosimilar) were the only short-acting G-CSFs and pegfilgrastim (Neulasta®) was the only long-acting G-CSF described in eligible studies. Outcomes of interest were FN, FN-related hospitalization, and other FN-related complications (death, chemotherapy dose delays and reductions, antimicrobial treatment, severe neutropenia, and costs and resource use).

Results: Of 1,259 unique records identified, 18 real-world observational studies met predefined inclusion criteria; 15 were retrospective studies, and 3 were prospective studies. Multiple tumor types, chemotherapy regimens, and geographical regions were included. Seven studies provided statistical comparisons of the risk of FN; risk of FN among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in 3 studies, numerically lower in 3 studies, and numerically higher in 1 study. Six studies provided statistical comparisons of the risk of FN-related hospitalization; risk of FN-related hospitalization among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in all 6 studies, though some variation was seen in subanalyses. Data for other outcomes were sparse with available results being generally consistent with the results seen for risk of FN and FN-related hospitalization.

Conclusions: Based on the findings from this review of real-world comparative effectiveness studies, risks of FN and FN-related complications were generally lower for prophylaxis with pegfilgrastim versus prophylaxis with short-acting G-CSFs.

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