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Supportive Care in Cancer : Official... Nov 2021Multiple myeloma (MM) survival rates have been substantially increased thanks to novel agents that have improved survival outcomes and shown better tolerability than... (Review)
Review
Multiple myeloma (MM) survival rates have been substantially increased thanks to novel agents that have improved survival outcomes and shown better tolerability than treatments of earlier years. These new agents include immunomodulating imide drugs (IMiD) thalidomide and lenalidomide, the proteasome inhibitor bortezomib (PI), recently followed by new generation IMID pomalidomide, monoclonal antibodies daratumumab and elotuzumab, and next generation PI carfilzomib and ixazomib. However, even in this more promising scenario, febrile neutropenia remains a severe side effect of antineoplastic therapies and can lead to a delay and/or dose reduction in subsequent cycles. Supportive care has thus become key in helping patients to obtain the maximum benefit from novel agents. Filgrastim is a human recombinant subcutaneous preparation of G-CSF, largely adopted in hematological supportive care as "on demand" (or secondary) prophylaxis to recovery from neutropenia and its infectious consequences during anti-myeloma treatment. On the contrary, pegfilgrastim is a pegylated long-acting recombinant form of granulocyte colony-stimulating factor (G-CSF) that, given its extended half-life, can be particularly useful when adopted as "primary prophylaxis," therefore before the onset of neutropenia, along chemotherapy treatment in multiple myeloma patients. There is no direct comparison between the two G-CSF delivery modalities. In this review, we compare data on the two administrations' modality, highlighting the efficacy of the secondary prophylaxis over multiple myeloma treatment. Advantage of pegfilgrastim could be as follows: the fixed administration rather than multiple injections, reduction in neutropenia and febrile neutropenia rates, and, finally, a cost-effectiveness advantage.
Topics: Antineoplastic Combined Chemotherapy Protocols; Febrile Neutropenia; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Multiple Myeloma; Polyethylene Glycols; Recombinant Proteins
PubMed: 33990881
DOI: 10.1007/s00520-021-06266-x -
Current Drug Targets 2022Pegfilgrastim-apgf (nyvepria) was currently approved by FDA for the treatment of febrile neutropenia associated with non-myeloid malignancies receiving myelosuppressive... (Review)
Review
Pegfilgrastim-apgf (nyvepria) was currently approved by FDA for the treatment of febrile neutropenia associated with non-myeloid malignancies receiving myelosuppressive anticancer drugs. It was developed by Pfizer, USA. It is a PEGylated leukocyte growth-stimulating factor indicated to reduce the incidence of febrile neutropenia in patients receiving anticancer drugs. Nyvepria is biosimilar to pegfilgrastim, approved by FDA on June 10, 2020. It is the fourth FDA-approved drug for the treatment of infection exhibiting febrile neutropenia. This review abridges the indicators in the development of nyvepria foremost to approval for the treatment of febrile neutropenia (FN), a biosimilar regulatory framework, and current updates on the clinical trials (CTs).
Topics: Antineoplastic Combined Chemotherapy Protocols; Biosimilar Pharmaceuticals; Chemotherapy-Induced Febrile Neutropenia; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Polyethylene Glycols; United States; United States Food and Drug Administration
PubMed: 35400340
DOI: 10.2174/1389450123666220408101152 -
BioDrugs : Clinical Immunotherapeutics,... Jun 2020Febrile neutropenia (FN) is a serious complication of chemotherapy, which can cause significant morbidity and mortality, result in dose delays and reductions and,... (Review)
Review
Febrile neutropenia (FN) is a serious complication of chemotherapy, which can cause significant morbidity and mortality, result in dose delays and reductions and, ultimately, reduce cancer survival. Over the past decade, the availability of biosimilar filgrastim (short-acting granulocyte colony-stimulating factor [G-CSF]) has transformed patient access, with clear evidence of clinical benefit at preventing FN at reduced costs. In 2019, seven biosimilar pegfilgrastims (long-acting G-CSFs) were licensed, creating optimal market conditions and choice for prescribers. FN affects up to 117 per 1000 cancer patients, with mortality rates in the range of 2-21%. By reducing FN incidence and improving chemotherapy relative dose intensity (RDI), G-CSF has been associated with a 3.2% absolute survival benefit. Guidelines recommend primary prophylaxis and that filgrastim be administered for 10-14 days, while pegfilgrastim is administered once per cycle. When taken according to the guidelines, pegfilgrastim and filgrastim are equally effective. However, in routine clinical practice, filgrastim is often under-dosed (< 7 days) and has been shown to be inferior to pegfilgrastim at reducing FN incidence, hospitalisations and maintaining RDI. Once-per-cycle administration with pegfilgrastim might also aid patient adherence. The introduction of biosimilar pegfilgrastim should instigate a rethink of neutropenia management. Biosimilar pegfilgrastim offers countries using biosimilar filgrastim opportunities to improve adherence and thus cancer survival, whilst offering economic benefits for countries using reference pegfilgrastim. These benefits can be realised in full if biosimilar pegfilgrastim becomes part of routine clinical practice supported by drug and therapeutic committees implementing guidelines with multidisciplinary support in the hospital.
Topics: Antineoplastic Agents; Biosimilar Pharmaceuticals; Chemotherapy-Induced Febrile Neutropenia; Filgrastim; Humans; Neoplasms; Polyethylene Glycols
PubMed: 32232676
DOI: 10.1007/s40259-020-00411-4 -
Future Oncology (London, England) Jun 2019Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. The development and use of biosimilar agents help to rationalize healthcare... (Review)
Review
Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. The development and use of biosimilar agents help to rationalize healthcare expenditure and improve access to modern therapies to all who need them. This review focuses on pegfilgrastims with important role in oncology supportive care. RGB-02 (Gedeon Richter) is a proposed biosimilar to pegylated granulocyte-colony stimulating factor (Neulasta, Amgen) with sustained release properties. The clinical analyses in three randomized clinical studies provided comparative data between RGB-02 and Neulasta, in a Phase III study patients receiving docetaxel-doxorubicin chemotherapy treatment equivalence was found. No difference was detected in any safety measure including immunogenicity; treatment switch, from the reference product to RGB-02 proved safe. Long-acting pegylated filgrastim RGB-02 has successfully accomplished various steps of biosimilar development.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biosimilar Pharmaceuticals; Chemotherapy-Induced Febrile Neutropenia; Drug Approval; Economics, Pharmaceutical; Europe; Filgrastim; Humans; Leukocyte Count; Neoplasms; Neutrophils; Polyethylene Glycols; Treatment Outcome; United States
PubMed: 31210542
DOI: 10.2217/fon-2018-0891 -
BMJ Case Reports Jun 2021
Topics: Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Polyethylene Glycols; Recombinant Proteins; Vasculitis
PubMed: 34083201
DOI: 10.1136/bcr-2021-243757 -
Cancer Treatment and Research... 2021Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving... (Review)
Review
Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving chemotherapy. Pegfilgrastim is recommended for FN prophylaxis in patients with non-myeloid malignancies receiving a high-risk chemotherapy regimen, or an intermediate-risk regimen if one or more risk factors are present. The guidelines highlight the patient characteristics and chemotherapy regimens for solid tumors and hematologic malignancies that may influence a patient's overall risk of FN and may benefit from pegfilgrastim support. This review aimed to evaluate how pegfilgrastim use in patients with cancer receiving myelosuppressive chemotherapy in routine clinical practice aligns with evidence-based US guidelines. Examination of the literature revealed widespread deviation in relation to under- and over-prescribing, and timing of administration in US clinical practice. Pegfilgrastim is often over-prescribed in patients receiving palliative chemotherapy and those at low risk of FN. Potential under-prescribing of pegfilgrastim was also observed. In this literature search, data that appear to support same-day administration of pegfilgrastim were from uncontrolled studies that were limited in size. Analyses of healthcare claims data clearly favored next-day use, with statistically significant increases in FN incidence among patients receiving same-day pegfilgrastim versus those treated 1-4 days post-chemotherapy. Earlier-than-recommended administration typically occurs at the physician's discretion where next-day administration might present barriers to the patient receiving supportive therapy.There is a need to ensure appropriate prescribing to optimize patient outcomes, as deviation from the guideline recommendations was associated with increased incidence of FN and hospitalization.
Topics: Filgrastim; Guideline Adherence; Humans; Medication Adherence; Neutropenia; Polyethylene Glycols; United States
PubMed: 34655862
DOI: 10.1016/j.ctarc.2021.100466 -
Expert Opinion on Biological Therapy 2015Neutropenia and febrile neutropenia are the most common and most severe bone marrow toxicities of chemotherapy. Recombinant granulocyte-colony stimulating factors... (Review)
Review
INTRODUCTION
Neutropenia and febrile neutropenia are the most common and most severe bone marrow toxicities of chemotherapy. Recombinant granulocyte-colony stimulating factors (G-CSFs), both daily (filgrastim and biosimilars, and lenograstim) and long-acting (pegfilgrastim and lipegfilgrastim) formulations, are currently available to counteract the negative consequences of these side effects.
AREAS COVERED
The purpose of this article is to review the physiopathology of chemotherapy-induced febrile neutropenia and its consequences, and the current evidence regarding the pharmacological properties, clinical efficacy and cost-effectiveness of pegfilgrastim as a strategy to prevent chemotherapy-induced febrile neutropenia in patients with solid tumors.
EXPERT OPINION
Chemotherapy-induced febrile neutropenia and its complications are still a major health-care concern, and the inappropriate employment of G-CSFs in clinical practice can partially explain its burden. Pegfilgrastim has pharmacological advantages over daily G-CSFs that makes it easily administrable, thus reducing the chance of incorrect delivery. The once-per-cycle administration might explain the findings derived from observational studies suggesting a possible superior efficacy of pegfilgrastim over daily G-CSFs. For patients at higher risk of failure with daily G-CSF prophylaxis (e.g. risk of non-compliance, difficulties on performing regular hemograms, high risk of developing febrile neutropenia), pegfilgrastim might be the most appropriate option.
Topics: Animals; Antineoplastic Agents; Biosimilar Pharmaceuticals; Chemotherapy-Induced Febrile Neutropenia; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Immunotherapy, Adoptive; Lenograstim; Neoplasms; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 26488491
DOI: 10.1517/14712598.2015.1101063 -
Bone Marrow Transplantation May 2009To date, G-CSF is the most favoured cytokine administered for PBSC mobilization because of its great efficacy and lack of serious toxicity. Recently, a pegylated... (Review)
Review
To date, G-CSF is the most favoured cytokine administered for PBSC mobilization because of its great efficacy and lack of serious toxicity. Recently, a pegylated filgrastim (pegfilgrastim) has been introduced. Attachment of the polyethylene glycol (PEG) moiety reduces renal excretion and masks proteolytic cleavage sites resulting in elevated G-CSF serum levels for up to 14 days after a single injection. As single-dose pegfilgrastim had similar effects in the prophylaxis of chemotherapy-induced neutropenia as the daily administration of the unconjugated drug, its capability for the mobilization of haematopoietic stem and progenitor cells has been assessed and presented to be at least equal to that of conventional G-CSF. Administration of pegfilgrastim following high-dose therapy and autologous blood SCT (BSCT) shortened the time to myeloid recovery as seen in conventional G-CSF. Plasma G-CSF levels were about 1 log higher with pegfilgrastim, but in the setting of autologous BSCT this did not translate into a faster haematopoietic recovery. Only few data exist on the biological effects of pegfilgrastim. Still, these data suggest that pegfilgrastim-stimulation results in different functional properties of haematopoietic stem and progenitor cells compared with G-CSF.
Topics: Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Kinetics; Polyethylene Glycols; Recombinant Proteins; Transplantation, Autologous
PubMed: 19308043
DOI: 10.1038/bmt.2009.59 -
Expert Review of Pharmacoeconomics &... Dec 2012For oncology patients, febrile neutropenia (FN) can be a serious and costly toxicity of chemotherapy, often forcing a reduction in chemotherapy dose intensity and/or... (Comparative Study)
Comparative Study Review
For oncology patients, febrile neutropenia (FN) can be a serious and costly toxicity of chemotherapy, often forcing a reduction in chemotherapy dose intensity and/or duration. Several therapeutic agents are used to reduce the occurrence of neutropenic episodes: granulocyte colony-stimulating factors (G-CSFs) and granulocyte-macrophage colony-stimulating factors. Appropriate administration of colony-stimulating factors reduces the risk of FN episodes and the costs associated with FN treatment. In the USA, the two most commonly used G-CSFs are filgrastim and the longer-acting pegfilgrastim. This pharmacoeconomic review of pegfilgrastim briefly considers some of the early research of G-CSFs, then focuses on the most recent comparative studies of pegfilgrastim against the backdrop of forthcoming US patent expiration for both products. The authors conclude with commentary on the market for pegfilgrastim in light of the growing debate surrounding the optimal selection of patients, treatment costs and future alternatives for the use of these agents in chemotherapy.
Topics: Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Costs; Economics, Pharmaceutical; Fever; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia; Patents as Topic; Patient Selection; Polyethylene Glycols; Recombinant Proteins; United States
PubMed: 23252353
DOI: 10.1586/erp.12.64 -
Journal of Oncology Pharmacy Practice :... Dec 2020Since 2018, several pegfilgrastim biosimilars were approved, which may affect insurance reimbursement. Guidelines recommend pegfilgrastim be administered the days... (Review)
Review
PURPOSE
Since 2018, several pegfilgrastim biosimilars were approved, which may affect insurance reimbursement. Guidelines recommend pegfilgrastim be administered the days following chemotherapy to prevent hematopoietic toxicity. To date, only the reference pegfilgrastim product has an available autoinjector-device. This has contributed to logistical issues in administering biosimilar agents per guideline recommendations. Administration on the same day as chemotherapy may be a potential alternative when logistical issues are present. This review will assess current evidence on this practice to inform clinical decisions. A comprehensive literature search was performed in PubMed/Medline for studies examining the administration of pegfilgrastim on the same day as chemotherapy. Several studies were identified, including a systematic review, retrospective reviews, and insurance claim data. Studies had significant limitations, and chemotherapy regimens and cancer types varied among studies. Studies showed inconsistent results in terms of incidence, duration, and severity of febrile neutropenia. In studies with patients with head and neck, urothelial, gynecologic, gastrointestinal, and prostate cancer, no difference in outcomes was detected or outcomes supported the feasibility of same-day administration. In patients with breast cancer, outcomes were worse with same-day administration. Outcomes were mixed in studies with non-Hodgkin's lymphoma, non-small cell lung cancer, and various solid tumors.
CONCLUSION
Administration of pegfilgrastim on the same day as chemotherapy may be safe and an acceptable alternative, if logistics prohibit a patient from receiving administration the days after chemotherapy. Clinicians should consider patient risk factors and prescribed chemotherapy regimens, along with available evidence when contemplating administration of same-day pegfilgrastim.
Topics: Biosimilar Pharmaceuticals; Filgrastim; Humans; Neoplasms; Polyethylene Glycols
PubMed: 32903142
DOI: 10.1177/1078155220956305