Authors: Liu, Zhimei¹; Doan, Quan V.¹; Malin, Jennifer²; Leonard, Robert³

Source: Applied Health Economics and Health Policy, Volume 7, Number 3, 1 September 2009 , pp. 193-205(13)

Publisher: Adis International

Abstract:

Background 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.

Objective To evaluate the cost effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the UK.

Methods 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 (£, 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.

Results Pegfilgrastim was cost saving compared with 11-day filgrastim (£3196 vs £4315). Compared with 6-day filgrastim, pegfilgrastim was associated with a cost of £4200 per FN event avoided, or £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 £441 (£3196 vs £2754) per person, yielding an incremental cost-effectiveness ratio (ICER) of £8075/LYG or £8526/QALY. In scenario 3, when all potential benefits of G-CSF were considered, the ICER became £3955/LYG or £4161/QALY. Results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim.

Conclusions In this UK analysis, pegfilgrastim appears to dominate 11-day use of filgrastim. The value of pegfilgrastim versus 6-day filgrastim at £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.

Document Type: Research article

Affiliations: 1: 1 Cerner LifeSciences, Beverly Hills, California, USA 2: 2 David Geffen School of Medicine at UCLA, Los Angeles, California, USA 3: 3 Imperial College NHS Trust, London, UK

Publication date: 2009-09-01

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