Refining the role of pegfilgrastim (a long-acting G-CSF) for prevention of chemotherapy-induced febrile neutropenia: consensus guidance recommendations

Abstract

PurposeChemotherapy-induced febrile neutropenia (FN) causes treatment delays and interruptions and can have fatal consequences. Current guidelines provide recommendations on granulocyte colony-stimulating factors (G-CSF) for prevention of FN, but guidance is unclear regarding use of short- vs long-acting G-CSF (e.g., filgrastim vs pegfilgrastim/lipegfilgrastim, respectively). An international panel of experts convened to develop guidance on appropriate use of pegfilgrastim for prevention of chemotherapy-induced FN.MethodsGuidance recommendations were developed following a literature review, survey, evaluation of current practice, and an expert meeting. Consensus was established using an anonymous Delphi-based approach.ResultsGuidance recommendations for prevention of treatment-associated FN were as follows: for treatment with curative intent, maintenance of dose intensity using G-CSF to prevent dose delays/reduction should be standard of care; for treatment-associated FN risk ≥ 20%, short-acting G-CSF/pegfilgrastim should be given from cycle 1 onwards; and for treatment-associated FN risk < 20%, short-acting G-CSF/pegfilgrastim should be given if factors suggest overall risk (including treatment-related and patient-related risk factors) is ≥ 20%. It was agreed that pegfilgrastim and 11 days’ filgrastim have similar efficacy and safety and that pegfilgrastim is preferred to < 11 days’ filgrastim (and may be preferred to ≥ 11 days’ filgrastim based on adherence and convenience); pegfilgrastim is not appropriate in weekly chemotherapy; in split-dose chemotherapy, pegfilgrastim is recommended 24 h after last chemotherapy dose; and during palliative chemotherapy, patient adherence and convenience may favor pegfilgrastim.ConclusionIn this era of targeted therapies, additional trials with G-CSF are still required. These recommendations should be used with existing guidelines to optimize pegfilgrastim use in clinical practice.

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

“…consecutive readings of > 38.0 °C for 2 h and an absolute neutrophil count (ANC) of < 0.5 × 10 9 /L, or expected to fall below 0.5 × 10 9 /L" [5]. It has been estimated that the incidence of FN might be as high as 117 cases per 1000 cancer patients [9]. FN causes a significant medical burden, with up to 30% of cases requiring inpatient hospital care and mortality rates in the range of 2-21% [5,10].…”

“…Primary prophylaxis with G-CSF should start with the first cycle of chemotherapy and continue throughout subsequent cycles [1,5,16,17]. ESMO recommends administration of filgrastim for around 10 days [5], whilst a recently published expert consensus recommends that pegfilgrastim should always be administered in preference to a duration of daily filgrastim of < 11 days [9]. Pegfilgrastim use is supported in different length chemotherapy cycles, including fortnightly, albeit data are more limited in patients receiving weekly regimens, where filgrastim might be preferred [9].…”

Incidence and risk factors for febrile neutropenia in Japanese patients with non-Hodgkin B cell lymphoma receiving R-CHOP: 2-year experience in a single center (STOP FN in NHL 2)

“…Most strategies for FN prevention using daily G-CSF and pegfilgrastim are based on data from overseas clinical studies [11]. Additionally, the frequency of FN in clinical studies may differ from that in routine clinical practice.…”

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

“…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]). The latter scenario seems more likely.…”