Abstract
Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) starting in the first and continuing in subsequent chemotherapy cycles when the risk of febrile neutropenia (FN) is ≥20% is recommended in the 2006 ASCO and EORTC clinical guidelines. Although the daily G-CSF filgrastim (Neupogen®, Amgen Inc.) and the long-acting G-CSF pegfilgrastim (Neulasta®, Amgen Inc.) are both commonly used, in practice filgrastim is often administered for shorter-than-recommended courses, eg, 6 days, which has been shown to be associated with less clinical efficacy. The purpose of this study was to evaluate the cost-effectiveness of primary prophylaxis using pegfilgrastim versus 6-day filgrastim in patients with aggressive non-Hodgkin’s lymphoma (NHL) receiving CHOP-21. Without G-CSF support, CHOP-21 is associated with 17%-50% FN risk. We constructed a decision-analytic model from a payer perspective with a life-time study horizon. Outcomes were measured as incremental cost-effectiveness ratios (ICERs) including cost per FN event avoided, cost per life-year-gained (LYG), or cost per quality-adjusted-life-year (QALY) saved. Model inputs including FN risk, FN case-fatality, relative dose intensity (RDI) of chemotherapy, impact of RDI on survival, and utility scores were obtained from a comprehensive literature review. Drug and drug administration costs were obtained from Center for Medicare and Medicaid Services. Cost for FN-related hospitalizations and subsequent medical costs were obtained from the literature. NHL mortality rates and other-cause mortality were based on data from US Surveillance Epidemiology and End Results and National Vital Statistics Reports. Sensitivity analyses were conducted on key variables. Our model simulated 3 clinical scenarios: Scenario 1 included the impact of prophylaxis with pegfilgrastim or filgrastim on FN risk, Scenario 2 included the impact of a difference in FN risk on FN-related mortality, and Scenario 3 included a differential impact on RDI and long-term survival. Extrapolating from the results of a meta-analysis and observational studies, it was estimated that pegfilgrastim decreased the absolute risk of FN by 12% compared with 6-day filgrastim (13.1% versus 25.1%) for a baseline FN risk of approximately 27.9%. Our results showed that compared with 6-day filgrastim, pegfilgrastim was associated with an ICER of $2,133/FN event avoided in Scenario 1, $4,869/LYG or $5,476/QALY saved in Scenario 2, and $1,805/LYG or $2,029/QALY saved in Scenario 3 (Table 1). Key factors influencing ICER estimates included relative risk of FN, cost of pegfilgrastim and filgrastim, and baseline FN risk. Varying these variables within plausible ranges, the ICERs did not exceed $100,000/QALY saved, a commonly cited threshold for judging cost-effectiveness in oncology. Our study suggested that primary prophylaxis with pegfilgrastim is cost-effective compared with filgrastim used for 6 days in NHL patients receiving CHOP-21.
Table 1: Cost-effectiveness of pegfilgrastim versus filgrastim Cost ($) Scenario 1 Scenario 2 (LY) Scenario 2 (QALY) Scenario 3 (LY) Scenario 3 (QALY) ICER, incremental cost-effectiveness ratio; LY, life-year; QALY, quality-adjusted life year; numbers may not match due to rounding errors Pegfilgrastim 15,608 13.1% 9.35 8.13 8.09 7.01 Filgrastim 15,352 25.1% 9.29 8.08 7.95 6.89 ICER --- $2,133 per FN event avoided $4,869/LY $5,476/QALY $1,805/LY $2,029/QALY
Primary extranodal non-Hodgkin’s lymphoma (NHL): the impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry