Prophylaxis Of Chemotherapy-induced Febrile Neutropenia Research Articles

Cost of Pegfilgrastim for the Prophylaxis of Chemotherapy-induced Febrile Neutropenia in Patients with Breast Cancer Receiving Perioperative Chemotherapy in Daily Practice in Japan: A Posthoc Analysis in a Single-center Retrospective Study.

This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.

Cost-effectiveness analysis of granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced febrile neutropenia in patients with breast cancer in Taiwan.

To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the perspective of Taiwan's National Health Insurance Administration. A Markov model was constructed to simulate the events that may occur during and after a high-risk chemotherapy treatment. Various G-CSF prophylaxis strategies and medications were compared in the model. Effectiveness data were derived from the literature and an analysis of the National Health Insurance Research Database (NHIRD). Cost data were obtained from a published NHIRD study, and health utility values were also obtained from the literature. Sensitivity analyses were performed to assess the uncertainty of the cost-effectiveness results. In the base-case analysis, primary prophylaxis with pegfilgrastim had an incremental cost-effectiveness ratio (ICER) of NT$269,683 per quality-adjusted life year (QALY) gained compared to primary prophylaxis with lenograstim. The ICER for primary prophylaxis with lenograstim versus no G-CSF prophylaxis was NT$61,995 per QALY gained. The results were most sensitive to variations in relative risk of febrile neutropenia (FN) for pegfilgrastim versus no G-CSF prophylaxis. Furthermore, in the probabilistic sensitivity analysis, at a willingness-to-pay threshold of one times Taiwan's gross domestic product per capita, the probability of being cost-effective was 88.1% for primary prophylaxis with pegfilgrastim. Our study suggests that primary prophylaxis with either short- or long-acting G-CSF could be considered cost-effective for FN prevention in breast cancer patients receiving high-risk regimens.

Effectiveness and Safety of Filgrastim (Neupogen™) versus Filgrastim-aafi (Nivestim™) in Primary Prophylaxis of Chemotherapy-Induced Febrile Neutropenia: An Observational Cohort Study.

Despite the demonstrated efficacy and safety of biosimilar filgrastim-aafi (Nivestim™), few studies have compared its use in real-life clinical practice to the originator filgrastim (Neupogen™). This study aimed to compare the effectiveness and safety of filgrastim and filgrastim-aafi for the primary prophylaxis of chemotherapy induced-febrile neutropenia in the real-life setting. A retrospective cohort study included all adult cancer patients at the King Hussein Cancer Centre requiring primary prophylaxis for chemotherapy-induced febrile neutropenia between 2014 and 2016. Two cohorts were selected: patients who received filgrastim and those who received filgrastim-aafi. The primary endpoint was the incidence of febrile neutropenia; the secondary endpoints were the incidence of adverse drug reactions (ADRs), hospital admissions due to febrile neutropenia, and the mean length of hospitalization. Chi-squared tests were performed to evaluate differences between groups. Logistic regression was conducted to adjust for confounding factors. A total of 268 patients were identified, with 88 in the filgrastim cohort and 180 in the filgrastim-aafi cohort; 64%were females. The mean age was 47 (±15) years. The incidence of febrile neutropenia was 21.6% in the filgrastim cohort and 15% in the filgrastim-aafi cohort (P = 0.179). No statistically significant differences were detected in the incidence of hospital admission (P = 0.551) or ADRs (P = 0.623) between the two cohorts. Upon adjusting for the confounding factors, results remained statistically insignificant. Filgrastim and filgrastim-aafi had comparable effectiveness and safety as primary prophylaxis for chemotherapy-induced febrileneutropenia. More extensive prospective studies with additional insight on the cost implications are required.

Development and content validation of the Satisfaction and Experience Questionnaire for Granulocyte Colony-Stimulating Factor (SEQ-G-CSF)

BackgroundSeveral options for granulocyte colony-stimulating factor (G-CSF) prophylaxis of chemotherapy-induced febrile neutropenia are available to patients worldwide. We have developed a novel patient-reported outcome measure, the Satisfaction and Experience Questionnaire for G-CSF (SEQ-G-CSF), to help understand patients’ perspectives of and satisfaction with different G-CSF options.ResultsThree oncology nurses and 40 adult oncology patients in the United States were enrolled and participated in focus group discussions to develop and refine the SEQ-G-CSF. Nurses had ≥ 5 years of experience treating oncology patients and were currently involved in the management of oncology patients receiving G-CSF prophylaxis. The patients had breast cancer, lung cancer, non-Hodgkin lymphoma, or prostate cancer (10 patients in each group) and were receiving G-CSF prophylaxis via injection or the on-body injector (OBI) device. The preliminary SEQ-G-CSF contained an item relevance questionnaire and three SEQ modules (sociodemographic, medical history, and G-CSF–related healthcare characteristics questionnaires). Twenty-one patients (53% of total sample size) discussed their experience and satisfaction with G-CSF. Their most common experiences were G-CSF effectiveness, convenience and benefits of the OBI, and relationships with healthcare providers. Side effects and having to undergo additional treatment were also reported. Satisfaction with aspects of G-CSF included the OBI and effectiveness of G-CSF treatment; dissatisfaction included inconvenience (having to return to the clinic the next day and administration of the injection) and the insurance approval process. The SEQ-G-CSF was finalized after three rounds of cognitive interviews and includes five domains related to general satisfaction (one item), treatment burden (four items), travel burden (two items), time burden (four items), and treatment compliance (two items).ConclusionsThe SEQ-G-CSF is a novel instrument that quantifies a patient’s experience and satisfaction with different G-CSF options using 13 easy-to-understand items. This study provides evidence for the content validity of SEQ-G-CSF. Although further psychometric testing is required, the SEQ-G-CSF may be a useful addition to clinical trials, observational studies, and clinical practice.

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer

The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N= 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. Patients (N= 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was-1.52% [95% confidence interval (CI):-3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI:-1.05 to 1.27) while for treatment-related hospitalisations it was-1.68% (95% CI:-2.73% to-0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference:-3.17%, 95% CI:-9.51% to 3.18%). Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. NCT02428114 and NCT02816164.

Primary Prophylaxis of Chemotherapy-Induced Febrile Neutropenia in Adult Patients with Lymphoproliferative Disorders - Clinical Experience in University Hospital of Split

Primary Prophylaxis of Chemotherapy-Induced Febrile Neutropenia in Adult Patients with Lymphoproliferative Disorders - Clinical Experience in University Hospital of Split

211P - A cost-utility analysis of administration schedules of G-CSF for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer: Economic evaluation alongside the REaCT-G trial

211P - A cost-utility analysis of administration schedules of G-CSF for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer: Economic evaluation alongside the REaCT-G trial

Abstract P5-15-19: Prophylaxis of chemotherapy-induced febrile neutropenia with biosimilar filgrastim: Description of patients, treatment patterns and outcomes in the MONITOR-GCSF study in the breast cancer cohort

Abstract Introduction: MONITOR-GCSF is a European prospective observational study of practice patterns and outcomes of patients treated with Sandoz' filgrastim (EP-2006) in the prophylaxis of chemotherapy-induced febrile neutropenia (CIN/FN). Objectives: To describe patients, treatment patterns of EP-2006, and outcomes in the breast cancer cohort of the MONITOR-GCSF study. Methods: Prospective observational study following 466 evaluable patients from 23 centers in Europe for up to 6 cycles within a single chemotherapy line including a total of 2714 cycles. Results: Median age was 56y (range 25-91); all but 3 patients were female. Table 1 presents chemotoxicity in terms of % FN risk and prophylaxis type. GCSF was correctly initiated as either primary or secondary prophylaxis per EORTC guideline recommendations (considering chemotherapy-related FN risk and patient-related factors) in 62% of patients. Eleven percent were undertreated, i.e., secondary prophylaxis when primary was indicated–either when CIN/FN risk &amp;gt;20% or when CIN/FN risk was 10-20% in combination with patient-related risk factors. Twenty-seven percent were overtreated, i.e., primary or secondary when not indicated–either primary prophylaxis in &amp;lt;10% risk of CIN/FN or in 10-20% risk of CIN/FN in the absence of risk factors, or secondary prophylaxis in &amp;lt;10% risk of CIN/FN in absence of prior CIN/FN. EP-2006 was started on average 2.8±2.6 days after chemotherapy was initiated and given for 4.9±2.1 days. Dosing was 45% at 30MIU/day, 55% at 48MIU/day. CIN (any grade) occurred in 12.0% of all cycles and 32.8% of patients had one or more episodes of CIN. 19.5% of patients had at least one episode of Grade 3 or 4 CIN of which 6.2% were febrile. CIN/FN-related hospitalizations were experienced by 5.2% of patients. CIN/FN-related chemotherapy disturbances (dose reduction, delay or cancellation) occurred in 9.4%. Table 1 n%Chemotherapy toxicity (risk of FN)&amp;gt;20%25053.8 10-20%17036.5 &amp;lt;10%459.7PhrophylaxisPrimary37279.8 Secondary9420.2Prophylaxis decision relative to guidelinesUndertreated5010.8 Correct28962.1 Overtreated12627.1 Conclusions: Variation in treatment with biosimilar GCSF in breast cancer patients is evident in terms of decision to treat with primary prophylaxis relative to guideline recommendations as well as day of initiation, duration and dose, yet incidence of CIN/FN and related events is low. Forthcoming analyses will determine whether variability in treatment is associated with differential outcomes. Citation Format: Pere Gascón, Matti Aapro, Heinz Ludwig, Mario Boccadoro, Carsten Bokemeyer, Matthew Turner, Michael Muenzberg, Ivo Abraham, Kris Denhaerynck, Karen MacDonald. Prophylaxis of chemotherapy-induced febrile neutropenia with biosimilar filgrastim: Description of patients, treatment patterns and outcomes in the MONITOR-GCSF study in the breast cancer cohort [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-19.

1555P - Biosimilar Filgrastim Initiation in Patients Enrolled in the Monitor G-CSF Observational Study Relative to EORTC Guidelines

ABSTRACT Introduction MONITOR G-CSF is a prospective observational study of practice patterns and outcomes for prophylaxis of chemotherapy-induced febrile neutropenia (FN) with biosimilar filgrastim (Zarzio®, Sandoz Biopharmaceuticals). Methods This analysis describes treatment initiation with biosimilar filgrastim in the 788 patients enrolled to date (target 1500) in the MONITOR G-CSF study relative to the 2010 EORTC G-CSF guidelines. Patients were enrolled at 134 centres (199 open) across 12 European countries. Results In this mainly female (62%) and older (61.6 ± 11.9 years) cohort with predominately solid tumours (79%), FN risk based on chemotherapy (CT) regimen was 20% in 39% of patients. All patients with Table 1 . All patients Prophylaxis (%) Initiation (%) Duration (%) Primary Secondary 24-72 h Days 5-8 3 days 5 days Tumour type: Oncology Haematology 70 70 30 30 56 24 30 56 16 11 42 47 CT toxicity: > 20% 10-20% 76 74 56 24 26 44 53 49 54 29 32 25 13 13 15 44 39 41 Table 2 . FN risk 10-20% Prophylaxis (%) Patient-related risk factors Primary Secondary Age >65 years 79 21 Advanced disease (Stage IV) 74 26 History of prior FN 29 71 No antibiotic prophylaxis 73 24 Poor performance (ECOG >2) 83 17 Female 76 24 Hb 70 30 Liver, renal or CV disease 72 28 One or more risks 74 26 Conclusions Variability exists in biosimilar filgrastim initiation by tumour type (day of initiation), CT toxicity and patient-related risk. About a quarter of patients with FN risk >20% or 10-20% in combination with other risk factors did not receive primary prophylaxis as recommended. The trend to initiate filgrastim in regimens with Disclosure M.S. Aapro: Member of the steering committee for Sandoz Biopharmaceuticals supported study. P. Gascon: Member of the steering committee for Sandoz Biopharmaceuticals supported study. H. Ludwig: Member of the steering committee for Sandoz Biopharmaceuticals supported study. On Speakers Bureau and advisory board for Amgen. C. Bokemeyer: Member of the steering committee for Sandoz Biopharmaceuticals supported study. M. Boccadoro: Member of the steering committee for Sandoz Biopharmaceuticals supported study. M. Turner: Employee of Sandoz Biopharmaceuticals. M. Muenzberg: Employee of Sandoz Biopharmaceuticals. K. Denhaerynck: Employee of Matrix 45. I. Abraham: Employee of Matrix 45. K. Macdonald: Employee of Matrix 45.

Update on the MONITOR-GCSF study of biosimilar filgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia in cancer patients: Protocol amendments

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of biosimilar filgrastim in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. The background and methodology of this study are described in an article published concurrently in this journal. As important amendments have been made to the protocol, and the purpose of the prior article was to serve as a resource for future referencing, we detail these amendments in this present article: explicit statement about the use of biosimilar filgrastim for both primary and secondary prophylaxis of chemotherapy-induced febrile neutropenia in the objectives and methodology of the study; length of observation; the addition of stage III and stage IV ovarian cancer and multiple myeloma to the tumor types studied; and the deletion of dose dense chemotherapy regimens as an exclusion criterion.

Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?

Updated international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor (G-CSF) in supporting delivery of myelosuppressive chemotherapy. G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia (FN) due to regimen and individual patient factors is ≥20%, for supporting dose-dense and dose-intense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes. Indeed, there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy. Predictive tools that can help target those patients who are most at risk of FN are now becoming available. Recent analyses have shown that, by reducing the risk of FN and chemotherapy dose delays and reductions, G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative settings. Accumulating data from ‘real-world’ clinical practice settings indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection. A single dose of PEGylated G-CSF (pegfilgrastim) may provide a more effective, as well as a more convenient, alternative to daily G-CSF. Prospective studies are needed to validate the importance of delivering the full dose intensity of standard chemotherapy regimens, with G-CSF support where appropriate, across a range of settings. These studies should also incorporate prospective evaluation of risk stratification for neutropenia and its complications.

Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia

The hematopoietic growth factors (HGFs) are a family of glycoproteins which plays a major role in the proliferation, differentiation, and survival of primitive hematopoietic stem and progenitor cells, and in the functions of some mature cells. More than 20 different molecules of HGF have been identified. Among them, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been demostrated to be effective in reducing the incidence of febrile neutropenia when administered inmediately after chemotherapy and as supportive therapy in patients undergoing bone marrow transplantation. Chemotherapy used for treatment of cancer often causes neutropenia, which may be profound, requiring hospitalization, and leading to potentially fatal infection. The uses of the recombinant human hematopoietic colony-stimulating factors G-CSF and GM-CSF for treatment and prophylaxis of chemotherapy-induced febrile neutropenia will be reviewed here.