Systematic Review and Meta-analysis of Short- versus Long-Acting Granulocyte Colony-Stimulating Factors for Reduction of Chemotherapy-Induced Febrile Neutropenia

Abstract

IntroductionShort- and long-acting granulocyte-colony stimulating factors (G-CSFs) are approved for the reduction of febrile neutropenia. A systematic literature review was performed to identify randomized controlled trials (RCTs) and non-RCTs reporting the use of G-CSFs following chemotherapy treatment.MethodsMedline®/Medline in-process, Embase®, and the Cochrane Library were searched for studies published between January 2003 and June 2016. A hand-search of relevant conference proceedings was conducted for meetings held between 2012 and 2016. Eligible studies were restricted to those reporting a direct, head-to-head comparison of short- versus long-acting G-CSFs for reduction of chemotherapy-induced febrile neutropenia. Risk-of-bias assessments were performed for full publications only.ResultsThe search strategy yielded 4044 articles for electronic screening. Thirty-six publications were evaluated for the meta-analysis: 11 of 12 RCTs and 2 of 24 non-RCTs administered doses of the short-acting G-CSF filgrastim for ≥ 7 days. In RCT studies, there was no statistically significant difference in outcomes of interest between short- and long-acting G-CSFs. In non-RCTs, the overall risk was lower with long-acting G-CSF than with short-acting G-CSF for incidence of febrile neutropenia [overall relative risk (RR) = 0.67, P = 0.023], hospitalizations (overall RR = 0.68, P < 0.05), and chemotherapy dose delays (overall RR = 0.68, P = 0.020).ConclusionsOverall, the weight of evidence from RCTs indicates little difference in efficacy between the short- and long-acting G-CSFs if dosed according to recommended guidelines. There is some evidence for greater efficacy for long-acting G-CSFs in non-RCTs, which may be a result of under-dosing of short-acting G-CSFs in general practice in real-world usage.FundingHospira Inc, which was acquired by Pfizer Inc in September 2015, and Pfizer Inc.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0798-6) contains supplementary material, which is available to authorized users.

Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure

“…This narrative review was developed by oncologists (MA, PC and PG) and a pharmacist (AV) who are experts in G-CSF and biosimilars and have published widely on the subject matter. Two of the authors (PC and PG) have recently published a systematic review and meta-analysis of all trials of G-CSF or pegfilgrastim for both randomised and nonrandomised comparisons using Cochrane methodology [4]. A further non-systematic review of the relevant literature in PubMed and the Cochrane Library was undertaken, which was supplemented by studies identified by the authors.…”

“…Numerous studies have compared the efficacy and safety of pegfilgrastim and filgrastim [4,15,[30][31][32]. A recent metaanalysis identified 36 studies that reported a direct, headto-head comparison of pegfilgrastim versus filgrastim [4]. In 12 RCTs, the relative risk (RR) of developing FN was lower for pegfilgrastim compared with filgrastim, but the difference was not statistically significant (0.86; p = 0.226).…”

“…FN further reduces cancer patient survival rates through delays, dose reductions and discontinuations of chemotherapy schedules [2,3]. As well as being a medical emergency with significant clinical burden, the economic burden of FN, particularly related to hospitalisations, is substantial [4,5]. Granulocyte colonystimulating factors (G-CSFs) have been proven effective in reducing the incidence of FN and are recommended for the prevention of chemotherapy-induced neutropenia in international guidelines [1,5].…”

“…Granulocyte colonystimulating factors (G-CSFs) have been proven effective in reducing the incidence of FN and are recommended for the prevention of chemotherapy-induced neutropenia in international guidelines [1,5]. There are two main types of G-CSF: filgrastim, which is administered daily during the chemotherapy cycle, and pegfilgrastim, a pegylated form of filgrastim, which allows administration once per cycle [4]. Biosimilars of filgrastim have been available in Europe since 2008 [6].…”

Febrile neutropenia prophylaxis with short- and long-acting granulocyte colony-stimulating factors during treatment of solid tumours

“…In some studies (5) included in the analysis, the effectiveness of pegfilgrastim and filgrastim was compared, which in a combined analysis led to a statistically significant difference in favour of its long-acting form (HR 0.66, 95% CI 0.44-0.98) [15]. In turn, a meta-analysis by Cornes et al showed no significant difference in preventing febrile neutropaenia between long-and short-acting drugs (although numerically it was a small difference in favour of long-acting molecules [RR 0.86, 95% CI 0.68-1.10]), while it indicated an advantage of long-acting drugs both in preventing the reduction of cytotoxic drug dosage (RR 0.69, 95% CI 0.57-0.83) as well as delays in their administration (RR 0.70, 95% CI 0.62-0.79) [16]. It is difficult to say unequivocally whether these differences are due to the actual higher efficacy of long-acting forms of G-CSF or rather to the use of an overly low total dose of short-acting drugs (it is estimated that a single administration of pegfilgrastim 6 mg is equivalent to 11 administrations of filgrastim [17,18]).…”