Budget Saving Potential of Pegfilgrastim Biosimilar for the Treatment of Chemotherapy-Induced Febrile Neutropenia, in Italy

Patrizia Berto, Marco Bellone, Alice Sabinot, Carmine Pinto, Massimo Martino, Daniele Generali, Pier Luigi Carriero, Maria Domenica Sanna

DOI: https://doi.org/10.7175/fe.v23i1.1516


INTRODUCTION: Current Italian guidelines recommend prophylaxis with granulocyte colony-stimulating factors (G-CSFs) to reduce the risk of chemotherapy-induced febrile neutropenia (FN). The availability of G-CSF biosimilars represents an opportunity for savings in the Italian National Healthcare Service (NHS) delivery of care.

OBJECTIVE: To assess the cost saving potential associated with the introduction of pegfilgrastim biosimilars to local formularies, compared to the current G-CSF standard practice in Italy.

METHODS: A budget impact model was developed to compare the current standard practice of long-acting (LA) and short-acting (SA) G-CSFs use, with a future scenario in which the market share of LA G-CSFs grows due to the more advantageous administration schedule and price of pegfilgrastim biosimilar. The analysis included G-CSF treatment schedules, drug acquisition costs and costs of patient management including hospitalization and ambulatory care.

RESULTS: The introduction of pegfilgrastim biosimilar resulted in cumulative 3-year cost savings of € 59,650 and € 41,539 for FN prophylaxis in a potential cohort of 1000 patients with solid tumors and lymphomas, respectively.

CONCLUSIONS: The results indicate that the introduction of pegfilgrastim biosimilar is potentially associated with substantial cost savings for the Italian healthcare system.


Biosimilars; Budget Impact Analysis; Cost saving; Febrile neutropenia; Granulocyte colony stimulating factor (G-CSF)

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  • Aapro M, Boccia R, Leonard R, et al. Refining the role of pegfilgrastim (a long-acting G-CSF) for prevention of chemotherapy-induced febrile neutropenia: consensus guidance recommendations. Support Care Cancer 2017;25:3295-304; https://doi.org/10.1016/s0959-8049(17)30619-6
  • Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol 2016;27:111-8; https://doi.org/10.1093/annonc/mdw325
  • Wang L, Baser O, Kutikova L, et al. 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 2015;23:3131-3140; https://doi.org/10.1007/s00520-015-2686-9
  • Pettengell R, Schwenkglenks M, Leonard R, et al. Neutropenia occurrence and predictors of reduced chemotherapy delivery: results from the INC-EU prospective observational European neutropenia study. Support Care Cancer 2008;16:1299-1309; https://doi.org/10.1007/s00520-008-0430-4
  • Bennett CL, Djulbegovic B, Norris LB, et al. Colony-stimulating factors for febrile neutropenia during cancer therapy. New Engl J Med 2013;368:1131-39; https://doi.org/10.1056/NEJMct1210890
  • Aapro MS, Bohlius J, Cameron DA, et al. 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 2011;47:8-32; https://doi.org/10.1016/j.ejca.2010.10.013
  • LG AIOM, Gestione della tossicità ematopoietica in oncologia, Edizione 2019.
  • Crawford J, Armitage J, Balducci L, et al. Myeloid growth factors. J Natl Compr Canc Netw 2013;11:1266-90; https://doi.org/10.6004/jnccn.2013.0148
  • Lyman GH, Dale DC, Culakova E, et al. 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 2013;24:2475-84; https://doi.org/10.1093/annonc/mdt226
  • Kuderer NM, Dale DC, Crawford J, et al. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol 2007;25:3158-67; https://doi.org/10.1200/JCO.2006.08.8823
  • Lyman GH, Barron RL, Natoli JL, et al. Systematic review of efficacy of dose-dense versus non-dose-dense chemotherapy in breast cancer, non-Hodgkin lymphoma, and non-small cell lung cancer. Crit Rev Oncol Hematol 2012;81:296-308; https://doi.org/10.1016/j.critrevonc.2011.04.010
  • Cornes P, Gascon P, Chan S, et al. Systematic review and meta-analysis of short- versus long-acting granulocyte colony-stimulating factors for reduction of chemotherapy-induced febrile neutropenia. Adv Ther 2018;35:1816-29; https://doi.org/10.1007/s12325-018-0798-6
  • Mitchell S, Li X, Woods M, et al. Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: a systematic review. J Oncol Pharm Pract 2016;22:702-716; https://doi.org/10.1177/1078155215625459
  • Botteri E, Krendyukov A, Curigliano G. Comparing granulocyte colony-stimulating factor filgrastim and pegfilgrastim to its biosimilars in terms of efficacy and safety: a meta-analysis of randomised clinical trials in breast cancer patients. Eur J Cancer 2018;89:49-55; https://doi.org/10.1016/j.ejca.2017.10.034
  • Fagnani D, Isa L, Verga MF, et al. Granulocyte colony-stimulating factors used in clinical practice: PoloNord registry-based cohort Italian study. Tumori 2014;100:491-498; https://doi.org/10.1700/1660.18158
  • Rosti G, Lebboroni M, Cerchiari A, et al. Analisi di budget impact sull’utilizzo di pegfilgrastim nella profilassi della neutropenia febbrile in Italia. Farmeconomia e percorsi terapeutici 2011;12:119-127
  • Trotta F, Mayer F, Mecozzi A, et al. Impact of guidance on the prescription patterns of G-CSFs for the prevention of febrile neutropenia following anticancer chemotherapy: A population-based utilization study in the Lazio region. BioDrugs 2017;31:117-124; https://doi.org/10.1007/s40259-017-0214-9
  • Cornes P, Gascon P, Vulto AG, et al. Biosimilar Pegflgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure. BioDrugs 2020;34:255-263; https://doi.org/10.1007/s40259-020-00411-4
  • Wang W, Li E, Campbell K, et al. Economic Analysis on Adoption of Biosimilar Granulocyte Colony-Stimulating Factors in Patients with Nonmyeloid Cancer at Risk of Febrile Neutropenia Within the Oncology Care Model Framework. JCO Oncology Practice 2021;17:1139-1149; https://doi.org/10.1200/OP.20.00994
  • Tilleul PR, Rodgers-Gray BS, Edwards JO. Introduction of biosimilar pegfilgrastim in France: Economic analysis of switching from originator. J Oncol Pharm Practice 2020;0:1-12; https://doi.org/10.1177/1078155220962208
  • Ravasio R, Antonuzzo L, Danova, et al. Budget impact analysis of pegfilgrastim biosimilar in the treatment of febrile neutropenia in Italy. AboutOpen 2020;7:04-08; https://doi.org/10.33393/abtpn.2020.2030
  • Sullivan SD, Mauskopf JA, Augustovski F, et al. Budget impact analysis principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value Health 2014;17:5-14; https://doi.org/10.1016/j.jval.2013.08.2291
  • Almenar-Cubells D, Mayans J, Juan O, et al. Pegfilgrastim and daily granulocyte colony-stimulating Factor: Patterns of use and Neutropenia-related outcomes in cancer patients in Spain-results of the LEARN study. Eur J Cancer Care (Engl) 2009;18:280-286; https://doi.org/10.1111/j.1365-2354.2008.00959.x
  • PELGRAZ Summary of Product Characteristics. Available at https://www.ema.europa.eu/en/documents/product-information/pelgraz-epar-product-information_en.pdf (last accessed October 2018)
  • Green M, Koelbl H, Baselga J, et al. A randomized double-blind multicenter phase III study offixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003;14:29-35; https://doi.org/10.1093/annonc/mdg019
  • Grigg A, Solal-Celigny P, Hoskin P, et al. Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin’s lymphoma. Leuk Lymphoma 2003;44:1503-1508; https://doi.org/10.1080/1042819031000103953
  • Romieu G, Clemens M, Mahlberg R, et al. Pegfilgrastim supports delivery of FEC-100 chemotherapy in elderly patients with high-risk breast cancer: A randomized Phase 2 trial. Crit Rev Oncol Hematol 2007;64:64-72; https://doi.org/10.1016/j.critrevonc.2006.12.007
  • Almenar Cubells D, Bosch Roig C, Jiménez Orozco E, et al. Effectiveness of daily versus non‐daily granulocyte colony‐stimulating factors in patients with solid tumours undergoing chemotherapy: A multivariate analysis of data from current practice. Eur J Cancer Care (Engl) 2013;22:400-412; https://doi.org/10.1111/ecc.12043
  • Bondarenko I, Gladkov OA, Elsaesser R, et al. 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 2013;13:386; https://doi.org/10.1186/1471-2407-13-386
  • Chan A, Leng XZ, Chiang JY, et al. Comparison Of Daily Filgrastim And Pegfilgrastim To Prevent Febrile Neutropenia In Asian Lymphoma Patients. Asia Pac J Clin Oncol 2010;7:75-81; https://doi.org/10.1111/J.1743-7563.2010.01355.X
  • Bozzoli V, Tisi MC, Maiolo E, et al. Four doses of Unpegylated versus one dose of pegylated Filgrastim as supportive therapy IN R-CHOP-14 for elderly patients with Diffuse Large B-cell lymphoma. Br J Haematol 2015;169:787-794; https://doi.org/10.1111/bjh.13358
  • Link H, Illerhaus G, Martens UM, et al. 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 2021;29:2519-2527; https://doi.org/10.1007/s00520-020-05711-7
  • Lazzaro C, Bordonaro R, Cognetti F, et al. An Italian cost-effectiveness analysis OF paclitaxel albumin (nab-paclitaxel) versus conventional paclitaxel for metastatic breast cancer patients: The COSTANza study. Clinicoecon Outcomes Res 2013;5:125–135; https://doi.org/10.2147/ceor.s41850
  • Remunerazione prestazioni di assistenza ospedaliera per acuti, assistenza ospedaliera di riabilitazione e di lungodegenza postacuzie e di assistenza specialistica ambulatoriale. Decreto 10/2012 e pubblicato in GU Serie Generale n.23 del 28-1-2013
  • IMS Data. IMS MAT data on G-CSF up to September 2020.
  • Farmaci Biologici E Biosimilari. Scenari terapeutici e stima del risparmio per il Sistema Sanitario italiano. Centro Studi IQVIA Italia. Available at https://assobiotec.federchimica.it/docs/default-source/default-document-library/(iqvia)_farmaci_biologici_e_biosimilari.pdf?sfvrsn=853ad623_0 (Last accessed March 2019)
  • Guidotti E, Vinci B, Attanasio F, et al. Effective tools to manage biosimilars prescription: The Italian experience. Health Policy and Technology 2021;10:45-51; https://doi:org/10.1016/j.hlpt.2020.10.011
  • Aapro M, Cornes P, Abraham I. Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia. J Oncol Pharm Pract 2012;18:171-179. https://doi.org/10.1177/1078155211407367
  • Sun D, Andayani TM, Altyar A, et al. Potential cost savings from chemotherapy-induced febrile neutropenia with biosimilar filgrastim and expanded access to targeted antineoplastic treatment across the European Union G5 countries: a simulation study. Clin Ther 2015;37:842-857. https://doi.org/10.1016/j.clinthera.2015.01.011
  • Pinto L, Liu Z, Doan Q, et al. Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: a metaanalysis of randomized controlled trials. Curr Med Res Opin 2007;23:2283-2295; https://doi.org/10.1185/030079907X219599
  • Bond TC, Szabo E, Gabriel S, et al. Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events. J Oncol Pharm Pract 2018;24:412-423; https://doi.org/10.1177/1078155217714859
  • Molineux G. Pegfilgrastim: using pegylation technology to improve neutropenia support in cancer patients. Anticancer Drugs 2003;13:259-264; https://doi.org/10.1097/00001813-200304000-00002
  • Lambertini M, Ferreira AR, Del Mastro L, et al. Pegfilgrastim for the prevention of chemotherapy induced febrile neutropenia in patients with solid tumours. Expert Opin Biol Ther 2015;15:1799-1817; https://doi.org/10.1517/14712598.2015.1101063
  • Weycker D, Hackett J, Edelsberg JS, et al. Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization? Ann Pharmacother 2006;40:402-7; https://doi.org/10.1345/aph.1G516
  • Gascón P, Aapro M, Ludwig H, et al. Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study) Support Care Cancer 2016;24:911-925; https://doi.org/10.1007/s00520-015-2861-z
  • Aapro M, Ludwig H, Bokemeyer C, et al. Predictive modeling of the outcomes of chemotherapyinduced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study). Ann Oncol 2016;27:2039-2045; https://doi.org/10.1093/annonc/mdw309
  • Tornero Molina J, Lopéz Robledillo JC, Ruiz NC. Potential Benefits of the Self Administration of Subcutaneous Methotrexate with Autoinjector Devices for Patients: A Review. Drug Healthc Patient Saf 2021;13:81-94; https://doi.org/10.2147/DHPS.S290771
  • Gandell D. Mode of injection and treatment adherence: results of a survey characterizing the perspectives of health care providers and US women 18-45 years old. Patient Prefer Adherence 2019;13:351-61; https://doi.org/10.2147/PPA.S187120
  • Cox D, Stone J. Managing self-injection difficulties in patients with relapsing-remitting multiple sclerosis. J Neurosci Nurs 2016;38,167-71; https://doi:10.1097/01376517-200606000-00005
  • Fraser C, Morgante L, Hadjimichael O, et al. A prospective study of adherence to glatiramer acetate in individuals with multiple sclerosis. J Neurosci Nurs 2004;36:120-129; https://doi.org/10.1097/01376517-200406000-00002
  • Bayas A. Improving adherence to injectable disease-modifying drugs in multiple sclerosis. Expert Opin Drug Deliv 2013;10:285-287; https://doi.org/10.1517/17425247.2013.763793


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