Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review
Pegfilgrastim was introduced over a decade ago. Other long-acting granulocyte colony-stimulating factors (G-CSFs) have recently been developed. We systematically reviewed the efficacy, effectiveness and safety of neutropenia prophylaxis with long-acting G-CSFs in cancer patients receiving chemotherapy.
We performed a systematic literature search of the MEDLINE, EMBASE and Cochrane Library databases, and abstracts from key congresses. Studies of long-acting G-CSFs for prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) were identified by two independent reviewers. Abstracts and full texts were assessed for final inclusion; risk of bias was evaluated using the Cochrane’s tool. Effectiveness and safety results were extracted according to study type and G-CSF used.
Of the 839 articles identified, 41 articles representing different studies met the eligibility criteria. In five randomised controlled trials, 11 clinical trials and 17 observational studies across several tumour types and chemotherapy regimens, pegfilgrastim was used alone or compared with daily G-CSF, no G-CSF, no upfront pegfilgrastim or placebo. Studies generally reported lower incidence of CIN (4/7 studies), FN (11/14 studies), hospitalisations (9/13 studies), antibiotic use (6/7 studies) and adverse events (2/5 studies) with pegfilgrastim than filgrastim, no upfront pegfilgrastim or no G-CSF. Eight studies evaluated other long-acting G-CSFs; most (5/8) were compared to pegfilgrastim and involved patients with breast cancer receiving docetaxel-based therapy. Efficacy and safety profiles of balugrastim and lipegfilgrastim were comparable to pegfilgrastim in phase 3 studies. Efficacy and safety of other long-acting G-CSFs were mixed.
Pegfilgrastim reduced the incidence of FN and CIN compared with no prophylaxis. Most studies showed better efficacy and effectiveness for pegfilgrastim than filgrastim. Efficacy and safety profiles of lipegfilgrastim and balugrastim were similar to pegfilgrastim.
KeywordsBalugrastim Granulocyte colony-stimulating factor Lipegfilgrastim Neutropenia Pegfilgrastim Systematic review
We would like to thank Ryan Bishop and Iain Fotheringham from Oxford PharmaGenesis™ Ltd (UK) for providing assistance with designing and conducting the systematic review. Funding for this support was provided by Amgen (Europe) GmbH. We would also like to acknowledge James O’Kelly of Amgen Ltd for coordinating our research collaboration, for doing the second risk of bias assessment and for his valuable feedback on the manuscript.
All authors were involved in the design of the study. KA was responsible for the first draft of the protocol, which was critically reviewed, further developed and approved by all authors. KA performed the literature search, and collected and extracted the data. AMP was responsible for the risk of bias assessment and the first draft of the manuscript. KA and AMP were responsible for the second draft. All authors contributed to data interpretation, critically reviewed all manuscript versions and approved the final version.
Conflicts of interest
AMP’s institution of employment receives unrestricted scientific/educational grants from Amgen. KA is an employee of Oxford PharmaGenesis™ Ltd, which has received project funding from Amgen. RP received honoraria from Amgen and Roche. GvM receives research funding from Amgen and Teva and served on an advisory board for Amgen. MS’s institution of employment receives unrestricted scientific/educational grants from Amgen and he has served on advisory boards for Amgen. ZS is an employee of Amgen and owns stock and stock options in the company.
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