Long-acting Granulocyte Colony-stimulating Factor Research Articles

Pattern of utilization of pegfilgrastim in patients with chemotherapy-induced neutropenia: A retrospective analysis of administrative claims data

9624 Background: Pegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) used to prevent or treat febrile neutropenia associated with myelosuppressive anticancer therapies. According to the prescribing information, pegfilgrastim should not be administered within 14 days before or 24 hours after cytotoxic chemotherapy because of the potential for myeloid toxicity. This study examined use patterns of pegfilgrastim in real-life practice. Methods: Analysis of health insurance claims data in 2000- 2007 from > 35 large health plans across the US was conducted. Patients who had a cancer diagnosis and chemotherapy within 120 days of their first pegfilgrastim injection were identified. The proportion of pegfilgrastim injections that were followed by administration of chemotherapy within 11 and 9 days was calculated. Analysis was also stratified by cancer type [Non-Hodgkin's lymphoma (NHL), lung, breast]. Results: A total of 13,526 cancer patients received 57,118 pegfilgrastim injections. NHL, lung, and breast cohorts comprised 2,722, 2,772, and 4,955 patients, respectively. Mean age (SD) was 55.0 (11.6) and women represented 65.9% of study population. Among all cancer types, 19.2% of pegfilgrastim injections had a chemotherapy claim within the following 11 days. This pattern of use was the highest in NHL (18.9%), followed by lung (17.1%), and breast (16.2%). Similar results were observed in the 9-day sensitivity analysis (see Table ). Conclusions: Based on the retrospective analysis of this administrative claims database, the use of pegfilgrastim within 11 days of an administration of chemotherapy was observed in 15–20% of cases which is inconsistent with the recommended guidelines. Pegfilgrastim use in these situations may have the potential to increase sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. Further research is being conducted to assess the related clinical and economic impact of this pattern of usage. [Table: see text] [Table: see text]

A Pharmacokinetic and Dose Escalation Study of Pegfilgrastim (KRN125) in Lung Cancer Patients with Chemotherapy-induced Neutropenia

The aim of this study was to investigate the safety, pharmacokinetic and pharmacodynamic profiles of pegfilgrastim (KRN125), a long-acting granulocyte colony-stimulating factor, in lung cancer patients with chemotherapy-induced neutropenia. Eighteen Japanese lung cancer patients who had experienced severe neutropenia (absolute neutrophil counts <0.5 x 10(9) cells/l) were enrolled. Six patients were sequentially enrolled in each pegfilgrastim dose cohort (dose levels of 30, 60 or 100 microg/kg). Patients received the same chemotherapy regimen as in their previous cycle and pegfilgrastim was injected subcutaneously the day after chemotherapy ended in each treatment cycle. Pharmacokinetic, pharmacodynamic and safety analyses were performed. Dose-limiting toxicity and serious adverse events related to pegfilgrastim were not observed in any patients. Pegfilgrastim antibodies were not detected. Maximum serum concentrations and area under the serum concentration-time curves of pegfilgrastim were dependent on the pegfilgrastim dose in a non-linear manner. Of the 18 patients, severe neutropenia occurred in 4 (22.2%), and, of these, 1 patient (5.5%) required rescue treatment by filgrastim. A single dose of pegfilgrastim increases the serum concentration of pegfilgrastim for several days in a dose-dependent manner and is not associated with significant toxicity. Good efficacy of pegfilgrastim for the prevention of severe neutropenia was observed at all dose levels. Based on these data, further studies are warranted to determine the recommended dose of pegfilgrastim for Japanese patients with chemotherapy-induced neutropenia.

Cost-Effectiveness of Primary Prophylaxis with Pegfilgrastim Versus Filgrastim in Non-Hodgkin's Lymphoma Patients Receiving CHOP-21.

Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) starting in the first and continuing in subsequent chemotherapy cycles when the risk of febrile neutropenia (FN) is ≥20% is recommended in the 2006 ASCO and EORTC clinical guidelines. Although the daily G-CSF filgrastim (Neupogen®, Amgen Inc.) and the long-acting G-CSF pegfilgrastim (Neulasta®, Amgen Inc.) are both commonly used, in practice filgrastim is often administered for shorter-than-recommended courses, eg, 6 days, which has been shown to be associated with less clinical efficacy. The purpose of this study was to evaluate the cost-effectiveness of primary prophylaxis using pegfilgrastim versus 6-day filgrastim in patients with aggressive non-Hodgkin's lymphoma (NHL) receiving CHOP-21. Without G-CSF support, CHOP-21 is associated with 17%-50% FN risk. We constructed a decision-analytic model from a payer perspective with a life-time study horizon. Outcomes were measured as incremental cost-effectiveness ratios (ICERs) including cost per FN event avoided, cost per life-year-gained (LYG), or cost per quality-adjusted-life-year (QALY) saved. Model inputs including FN risk, FN case-fatality, relative dose intensity (RDI) of chemotherapy, impact of RDI on survival, and utility scores were obtained from a comprehensive literature review. Drug and drug administration costs were obtained from Center for Medicare and Medicaid Services. Cost for FN-related hospitalizations and subsequent medical costs were obtained from the literature. NHL mortality rates and other-cause mortality were based on data from US Surveillance Epidemiology and End Results and National Vital Statistics Reports. Sensitivity analyses were conducted on key variables. Our model simulated 3 clinical scenarios: Scenario 1 included the impact of prophylaxis with pegfilgrastim or filgrastim on FN risk, Scenario 2 included the impact of a difference in FN risk on FN-related mortality, and Scenario 3 included a differential impact on RDI and long-term survival. Extrapolating from the results of a meta-analysis and observational studies, it was estimated that pegfilgrastim decreased the absolute risk of FN by 12% compared with 6-day filgrastim (13.1% versus 25.1%) for a baseline FN risk of approximately 27.9%. Our results showed that compared with 6-day filgrastim, pegfilgrastim was associated with an ICER of $2,133/FN event avoided in Scenario 1, $4,869/LYG or $5,476/QALY saved in Scenario 2, and $1,805/LYG or $2,029/QALY saved in Scenario 3 (Table 1). Key factors influencing ICER estimates included relative risk of FN, cost of pegfilgrastim and filgrastim, and baseline FN risk. Varying these variables within plausible ranges, the ICERs did not exceed $100,000/QALY saved, a commonly cited threshold for judging cost-effectiveness in oncology. Our study suggested that primary prophylaxis with pegfilgrastim is cost-effective compared with filgrastim used for 6 days in NHL patients receiving CHOP-21.Table 1:Cost-effectiveness of pegfilgrastim versus filgrastimCost ($)Scenario 1Scenario 2 (LY)Scenario 2 (QALY)Scenario 3 (LY)Scenario 3 (QALY)Pegfilgrastim15,60813.1%9.358.138.097.01Filgrastim15,35225.1%9.298.087.956.89ICER---$2,133 per FN event avoided$4,869/LY$5,476/QALY$1,805/LY$2,029/QALYICER, incremental cost-effectiveness ratio; LY, life-year; QALY, quality-adjusted life year; numbers may not match due to rounding errors

Safety and efficacy of pegfilgrastim in patients receiving myelosuppressive chemotherapy.

The major dose-limiting toxicity associated with myelosuppressive chemotherapy is neutropenia, which can be ameliorated with proactive administration of granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim is a long-acting G-CSF, recently approved by the Food and Drug Administration. The efficacy and safety of pegfilgrastim administered once/chemotherapy cycle have been evaluated in clinical trials involving patients treated with myelosuppressive chemotherapy for breast cancer, lung cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. Two pivotal phase III trials in patients with breast cancer showed that pegfilgrastim is as effective as filgrastim regarding the primary efficacy end point, which was duration of grade 4 (severe) neutropenia in cycle 1 of myelosuppressive chemotherapy. Secondary end points were the frequency of fever with neutropenia (febrile neutropenia), duration of neutropenia in cycles 2-4, depth of the absolute neutrophil count (ANC) nadir, and time to ANC recovery in cycles 1-4. Once/cycle pegfilgrastim 100 microg/kg or 6 mg was as safe and effective as daily filgrastim 5 microg/kg in reducing the frequency and duration of severe neutropenia. A trend toward a greater reduction in the overall frequency of febrile neutropenia with pegfilgrastim was observed. The availability of pegfilgrastim simplifies the use of prophylactic G-CSF, with the potential to increase patient convenience and adherence in management of chemotherapy-induced neutropenia.

Phantom of an outpatient service

<h3>Objective</h3> This study explored the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia (FN) in newly diagnosed patients with epithelial ovarian cancer (EOC). <h3>Methods</h3> Patients were randomised into a study group (long-acting G-CSF for all chemotherapy cycles) and a control group (short-acting G-CSF for first cycle and treatment per physician discretion for subsequent cycles) at a ratio of 1:2. The incidences of FN and myelosuppression and the number of clinical visits, medication doses, complete blood count (CBC) tests and adverse events were compared between the two groups. A regression model was used to determine the risk factors for FN. <h3>Results</h3> From 30 November 2018 to 1 April 2019, 84 cases were included in the final analysis; there were 24 (28.6%) and 60 (71.4%) patients in the study and control groups, respectively, and 605 chemotherapy cycles. The study group or chemotherapy cycles utilising long-acting G-CSF had significantly fewer utilisations and doses of short-acting G-CSF; clinical visits; CBC tests; and incidences of FN and myelosuppression; and less G-CSF-associated pain. The utilisation of G-CSF was the only independent factor for FN in a binary regression model. <h3>Conclusion</h3> Long-acting G-CSF could effectively reduce the incidences of FN and myelosuppression and had mild adverse effects in newly diagnosed patients with EOC receiving chemotherapy. <h3>Trial registration number</h3> NCT03740464.