The economic value of primary prophylaxis using pegfilgrastim compared with filgrastim in patients with breast cancer in the UK
ABSTRACT Febrile neutropenia (FN) is a serious adverse event associated with myelotoxic chemotherapy that predisposes patients to life-threatening bacterial infections. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) from the first cycle of chemotherapy is recommended by the 2006 American Society of Clinical Oncology, 2008 National Comprehensive Cancer Network and 2006 European Organisation for Research and Treatment of Cancer guidelines when the overall risk of FN is approximately 20% or higher. Once-per-cycle pegfilgrastim and daily filgrastim are two commonly used G-CSFs with different dosing schedules and associated costs.
To evaluate the cost effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the UK.
A decision-analytic model was constructed from the UK NHS perspective with a lifetime study horizon. The model simulated three clinical scenarios: scenario 1 assumed that pegfilgrastim and filgrastim had differential impact on the risk of FN; scenario 2 assumed additional differential impact on FN-related mortality; and scenario 3 assumed additional differential impact on chemotherapy relative dose intensity (RDI) with long-term survival effects. The base-case population included 45-year-old women with stage II breast cancer receiving four chemotherapy cycles, with an FN risk of approximately 20% or higher. Model inputs, including FN risk, FN case-fatality, RDI, impact of RDI on survival and utility scores, were based on a review of the literature and expert panel validation. Using data from the literature, it was estimated that the absolute risk of FN associated with pegfilgrastim was 5.5% lower than with 11-day filgrastim (7% vs 12.5%), and 10.5% lower than with 6-day filgrastim (7% vs 17.5%). Costs were taken from official price lists or the literature and included drugs, drug administration, FN-related hospitalizations and subsequent medical costs. Breast cancer mortality and all-cause mortality were obtained from official statistics. The main outcome measures were the costs ( pound, year 2006 values) per percentage decrease in (absolute) FN risk, per FN event avoided, per life-year gained (LYG), and per QALY gained. Model robustness was tested using deterministic and probabilistic sensitivity analyses.
Pegfilgrastim was cost saving compared with 11-day filgrastim ( pound 3196 vs pound 4315). Compared with 6-day filgrastim, pegfilgrastim was associated with a cost of pound 4200 per FN event avoided, or pound 42 per 1% decrease in absolute risk of FN, in scenario 1. In scenario 2, pegfilgrastim provided 0.055 more LYGs or 0.052 more QALYs at a minimal cost increase of pound 441 ( pound 3196 vs pound 2754) per person, yielding an incremental cost-effectiveness ratio (ICER) of pound 8075/LYG or pound 8526/QALY. In scenario 3, when all potential benefits of G-CSF were considered, the ICER became pound 3955/LYG or pound 4161/QALY. Results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim.
In this UK analysis, pegfilgrastim appears to dominate 11-day use of filgrastim. The value of pegfilgrastim versus 6-day filgrastim at pound 4161-8526/QALY was very favourable compared with the commonly used threshold in the UK. In this setting, primary prophylaxis with pegfilgrastim may be cost effective compared with filgrastim.
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ABSTRACT: Antineoplastic drugs for cancer are often associated with adverse events, which influence patients' physical health, quality of life and survival. However, the modelling of adverse events in cost-effectiveness analyses of antineoplastic drugs has not been examined. This article reviews published economic evaluations that include a calculated cost for adverse events of antineoplastic drugs. The aim is to identify how existing models manage four issues specific to antineoplastic drug adverse events: the selection of adverse events for inclusion in models, the influence of dose modifications on drug quantity and survival outcomes, the influence of adverse events on quality of life and the consideration of multiple simultaneous or recurring adverse events. A systematic literature search was conducted using MESH headings and key words in multiple electronic databases, covering the years 1999-2009. Inclusion criteria for eligibility were papers covering a population of adults with solid tumour cancers, the inclusion of at least one adverse event and the resource use and/or costs of adverse event treatment. From 4,985 citations, 26 eligible articles were identified. Studies were generally of moderate quality and addressed a range of cancers and treatment types. While the four issues specific to antineoplastic drug adverse events were addressed by some studies, no study addressed all of the issues in the same model. This review indicates that current modelling assumptions may restrict our understanding of the true impact of adverse events on cost effectiveness of antineoplastic drugs. This understanding could be improved through consideration of the selection of adverse events, dose modifications, multiple events and quality of life in cost-effectiveness studies.Applied Health Economics and Health Policy 10/2013; 11(6). DOI:10.1007/s40258-013-0058-5
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ABSTRACT: 5-fluorouracil, epirubicin, cyclophosphamide → docetaxel (FEC-D) has been associated with higher-than-expected rates of febrile neutropenia (FN) that meet the current guideline threshold of 20 % for primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF). We examined the cost-effectiveness of FEC-D with varying strategies of G-CSF prophylaxis from the perspective of the public payer in Ontario, Canada. A state-transition model was developed to compare three strategies: FEC-D with secondary prophylaxis (SP) only, PP starting with the first cycle of D, and PP starting with the first cycle of FEC. Analysis was conducted for a hypothetical cohort of 50-year-old early-stage breast cancer patients undergoing adjuvant chemotherapy, at a 10-year horizon. Results were expressed in quality-adjusted life-years (QALYs) and 2013 Canadian dollars. Costs and benefits were discounted at 5 %. Event rates, costs, and utilities were derived from the literature. One-way and probabilistic sensitivity analyses were conducted. Using filgrastim, the incremental cost-effectiveness ratios (ICERs) for starting PP with the first cycle of D and starting PP with the first cycle of FEC, compared to using SP only, were $57,886/QALY and $116,186/QALY, respectively. With pegfilgrastim, the ICERs for the same strategies were $90,735/QALY and $149,483/QALY. Compared to using filgrastim SP only, starting PP with D had a 24 % chance of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY, and a 99 % chance at a WTP threshold of $100,000/QALY. Results were sensitive to FN-related parameters, such as the risk of FN per cycle with D and the associated mortality, but were robust to uncertainty in parameters related to breast cancer, such as the utilities and hazard of relapse. FEC-D with PP starting with the first cycle of D is most likely to be cost-effective, especially with increased risk of FN and mortality from FN.Breast Cancer Research and Treatment 02/2015; DOI:10.1007/s10549-015-3309-3 · 4.20 Impact Factor
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ABSTRACT: Introduction: Granulocyte colony-stimulating factor (G-CSF; filgrastim) and its pegylated form (pegfilgrastim) are widely used to treat neutropenia associated with myelosuppressive chemotherapy and bone marrow transplantation, AIDS-associated or drug-induced neutropenia, and neutropenic diseases. G-CSF facilitates restoration of neutrophil counts, decreases incidence of infection/febrile neutropenia and reduces resource utilization. G-CSF is also widely used to mobilize peripheral blood stem cells for hematopoietic transplant. Areas covered: We review the therapeutic use, cost effectiveness and disease impact of G-CSF for neutropenia, development of G-CSF biosimilars and current next-generation discovery efforts. Expert opinion: G-CSF has impacted the treatment and survival of patients with congenital neutropenias. For chemotherapy-associated neutropenia, cost effectiveness and impact on survival are still unclear. G-CSFs are expensive and require systemic administration. Market entry of new biosimilars, some with enhanced half-life profiles, will probably reduce cost and increase cost effectiveness. There is no evidence that marketed or late development biosimilars display effectiveness superior to current G-CSFs. Second-generation compounds that mimic the activity of G-CSF at its receptor, induce endogenous ligand(s) or offer adjunct activity have been reported and represent attractive G-CSF alternatives, but are in preclinical stages. A significant therapeutic advance will require reduced depth and duration of neutropenia compared to current G-CSFs.Expert Opinion on Investigational Drugs 09/2013; DOI:10.1517/13543784.2013.838558 · 5.43 Impact Factor