Abstract
Purpose
We assessed the occurrence of neutropenia and febrile neutropenia (FN) and the associated healthcare resource in cancer patients receiving myelosuppressive chemotherapy in combination with pegfilgrastim versus lipegfilgrastim.
Methods
This is a retrospective analysis using a German health insurance claims database. Adults receiving chemotherapy with a prescription code for pegfilgrastim (n = 734) or lipegfilgrastim (n = 346) were observed over a 1-year follow-up period. Patient subgroups were analyzed according to cancer type and FN risk. FN risk was based on the chemotherapy regimen and any additional neutropenia risk factors. Outcomes were adjusted via regression analysis.
Results
Most patients were classified as high FN risk (70.0% pegfilgrastim; 65.6% lipegfilgrastim cohort). The mean age was 58.2 years in the pegfilgrastim cohort and 58.0 years in the lipegfilgrastim cohort, with more female patients than male patients (77.3% vs 79.8%, respectively), and the majority had breast cancer (64.9% and 68.8%, respectively). Overall, 10.0% and 10.4% of patients receiving pegfilgrastim or lipegfilgrastim experienced a neutropenia event (p = 0.82), with 4.4% and 3.5% of patients experiencing a FN event (p = 0.49). The mean neutropenia event-related healthcare costs were €604 and €441 for the pegfilgrastim and lipegfilgrastim cohorts; among patients with lymphoma, these costs were significantly greater (p = 0.03) with pegfilgrastim (€1,612) versus lipegfilgrastim (€382). The mean all-cause hospitalizations were significantly (p < 0.01) higher for lymphoma patients receiving pegfilgrastim (2.76) versus lipegfilgrastim (1.60).
Conclusion
Overall, patients treated with pegfilgrastim and lipegfilgrastim were comparable in terms of neutropenia occurrences in the 1-year follow-up. In patients with lymphoma, neutropenia event-related healthcare costs and all-cause hospitalizations were significantly higher with pegfilgrastim compared with lipegfilgrastim in this study; however, this should be interpreted with caution in light of the limited sample size and the absence of clinical information.
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Data availability
The data used in this study cannot be made available in the manuscript, the supplemental files, or in a public repository due to German data protection laws (Bundesdatenschutzgesetz). To facilitate the replication of results, anonymized data used for this study are stored on a secure drive at the Institute for Applied Health Research Berlin (InGef). Access to the data used in this study can only be provided to external parties under the conditions of the cooperation contract of this research project and can be assessed upon request, after written approval (info@ingef.de), if required.
Code availability
Not applicable.
References
Klastersky J, de Naurois J, Rolston K et al (2016) ESMO Guidelines Committee. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol 27(suppl 5):v111–v118. https://doi.org/10.1093/annonc/mdw325
Lyman GH, Dale DC, Culakova E et al (2013) The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol 24(10):2475–2484. https://doi.org/10.1093/annonc/mdt226
National Cancer Institute. Common terminology criteria for adverse advents v4.03 (Excel). June 14, 2010. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm
Smith TJ, Bohlke K, Lyman GH et al (2015) Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 33(28):3199–3212. https://doi.org/10.1200/JCO.2015.62.3488
Aapro MS, Bohlius J, Cameron DA et al (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47:8–32. https://doi.org/10.1016/j.ejca.2010.10.013
Aapro M, Boccia R, Leonard R et al (2017) Refining the role of pegfilgrastim (a long-acting G-CSF) for prevention of chemotherapy-induced febrile neutropenia: consensus guidance recommendations. Support Care Cancer 25(11):3295–3304. https://doi.org/10.1007/s00520-017-3842-1
National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines). Hematopoietic Growth Factors. Version 4, 2021. https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf
Wang Y, Chen L, Liu F et al (2019) Efficacy and tolerability of granulocyte colony-stimulating factors in cancer patients after chemotherapy: a systematic review and Bayesian network meta-analysis. Sci Rep 9(1):15374. https://doi.org/10.1038/s41598-019-51982-4
Buchner A, Lammerich A, Abdolzade-Bavil A et al (2014) Lipegfilgrastim: pharmacodynamics and pharmacokinetics for body-weight-adjusted and 6 mg fixed doses in two randomized studies in healthy volunteers. Curr Med Res Opin 30(12):2523–2533. https://doi.org/10.1185/03007995.2014.962131
Bondarenko I, Gladkov OA, Elsaesser R et al (2013) Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy. BMC Cancer 13:386. https://doi.org/10.1186/1471-2407-13-386
Gladkov OA, Buchner A, Bias P et al (2016) Chemotherapy-associated treatment burden in breast cancer patients receiving lipegfilgrastim or pegfilgrastim: secondary efficacy data from a phase III study. Support Care Cancer 24(1):395–400. https://doi.org/10.1007/s00520-015-2803-9
Link H, Illerhaus G, Martens UM et al (2021) Efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (B-NHL): results of the randomized, open-label, non-inferiority AVOID neutropenia study. Support Care Cancer 29:2519–2527. https://doi.org/10.1007/s00520-020-05711-7
Statistisches Bundesamt DESTATIS. Ergebnisse der Bevölkerungsfortschreibung auf Grundlage des Zensus 2011 [April 30, 2021]. https://www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Bevoelkerung/Bevoelkerungsstand/Tabellen/liste-zensus-geschlecht-staatsangehoerigkeit.html
Bundesministerium für Gesundheit. Kennzahlen der Gesetzlichen Krankenversicherung 2007 bis 2020. Kennzahlen und Faustformeln, https://www.bundesgesundheitsministerium.de/fileadmin/Dateien/3_Downloads/Statistiken/GKV/Kennzahlen_Daten/KF2021Bund_Juli_2021.pdf
Andersohn F, Walker J (2016) Characteristics and external validity of the German Health Risk Institute (HRI) Database. Pharmacoepidemiol Drug Saf 25(1):106–109. https://doi.org/10.1002/pds.3895
Quan H, Li B, Couris CM et al (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173(6):676–682. https://doi.org/10.1093/aje/kwq433
The International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification (ICD-10-GM). https://www.bfarm.de/EN/Code-systems/Classifications/ICD/ICD-10-GM/_node.html
Link H, Kerkmann M, Holtmann L, Ortner P (2019) Working Groups Supportive C, Medical Oncology within the German Cancer S. G-CSF guideline adherence in Germany, an update with a retrospective and representative sample survey. Support Care Cancer 27(4):1459–1469. https://doi.org/10.1007/s00520-018-4481-x
Einheitlicher Bewertungsmaßstab. https://www.kbv.de/html/online-ebm.php
Wang L, Baser O, Kutikova L et al (2015) The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer 23(11):3131–3140. https://doi.org/10.1007/s00520-015-2686-9
Bond TC, Mueller U, Barnes G et al (2015) Lipegfilgrastim for reduction of chemotherapy-induced neutropenia related events: a meta-analysis. Value Health 18:A434. https://doi.org/10.1016/j.jval.2015.09.1041
Kurbacher CM, Fietz T, Diel IJ et al (2015) NADIR: A non-interventional study on the prophylaxis of chemotherapy-induced neutropenia using lipegfilgrastim – first interim analysis. Oncol Res Treat 38(5):221–229. https://doi.org/10.1159/000381631
Akpo EIH, Jansen IR, Maes E, Simoens S (2017) Cost-utility analysis of lipegfilgrastim compared to pegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia in patients with stage ii–iv breast cancer. Front Pharmacol 8:614
Gao L, Li SC (2018) Cost-effectiveness analysis of lipegfilgrastim as primary prophylaxis in women with breast cancer in Australia: a modelled economic evaluation. Breast Cancer 25(6):671–680
Link H, Nietsch J, Kerkmann M, Ortner P (2016) Adherence to granulocyte-colony stimulating factor (G-CSF) guidelines to reduce the incidence of febrile neutropenia after chemotherapy–a representative sample survey in Germany. Support Care Cancer 24(1):367–376. https://doi.org/10.1007/s00520-015-2779-5
Acknowledgements
Editorial support was provided by Ketchum Inspired Science (London, UK), which was funded by Teva Pharmaceuticals Inc. The data analysis was performed in cooperation with Prof. Dr. Wolfgang Greiner and the Institute for Applied Health Research Berlin (InGef).
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The study was funded by Teva Pharmaceuticals Inc.
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Not applicable. No ethical approval and consent were necessary as this is a retrospective database study based on anonymized claims data.
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Competing interests
HL declares to have received personal fees from Accord Healthcare Limited, Europharma, Johnson & Johnson, Lindis-Blood Care, Mundipharma, Onkodin GmbH (onchemo.com), Pharmacosmos, Rhineland-Palatinate Medical Association (Mainz), Samsung Bioepis; SAP, Servier Deutschland GmbH, Shire Deutschland GmbH (Takeda Group), SIGAL SMS GmbH, Takeda, Hogg Robinson Germany, Teva, and Viatris. SF, MT, and SD are employees of Teva. JSH, DM, and CM are employees of Xcenda GmbH. Xcenda GmbH received consulting fees for the conduct of the analysis.
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Link, H., Thompson, S.F., Tian, M. et al. A comparative assessment of neutropenia events, healthcare resource use, and costs among cancer patients treated with lipegfilgrastim compared with pegfilgrastim in Germany. Support Care Cancer 30, 9317–9327 (2022). https://doi.org/10.1007/s00520-022-07353-3
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DOI: https://doi.org/10.1007/s00520-022-07353-3