Pegfilgrastim Prophylaxis Throughout Chemotherapy Is More Effective in Preventing Febrile Neutropenia in Breast Cancer (and More Costly)
Available data suggest that risk of febrile neutropenia is greatest during the first two cycles of chemotherapy in patients with breast cancer. In a study reported in the Journal of Clinical Oncology, Maureen J. Aarts of Maastricht University Medical Centre in the Netherlands, and colleagues evaluated the cost-effectiveness of primary prohylaxis with pegfilgrastim (Neulasta; pegylated granulocyte colony-stimulating factor [G-CSF]) covering the first two cycles vs all six cycles of chemotherapy in patients with breast cancer who were at risk of febrile neutropenia. They found that prophylaxis throughout chemotherapy is more effective in preventing febrile neutropenia and more costly, with an incremental cost-effectiveness ratio of €13,112 per patient with episodes of febrile neutropenia prevented.
Study Details
The analysis was conducted in 167 patients in a phase III trial comparing pegfilgrastim prophylaxis during all chemotherapy cycles (G-CSF 1–6 group; n = 84) vs the first two chemotherapy cycles only (G-CSF 1–2 group; n = 83) in patients with breast cancer who had > 20% risk of febrile neutropenia. The primary outcome was cost-effectiveness expressed as costs per patient with episodes of febrile neutropenia prevented, and the evaluation used a health-care perspective. Specific costs included delivered chemotherapy, prophylactic antibiotics, prophylactic G-CSF, all costs related to a period of febrile neutropenia (diagnostics, hospitalization, general practitioner or outpatients visits, and medication including transfusions), and all health-care costs for any other reason.
In the trial population, the G-CSF 1–6 group and the G-CSF 1–2 group were balanced for age (median, 50 years in both, 94% ≤ 65 years in both), Eastern Cooperative Oncology Group performance status of 0 or 1 (96% and 98%), neoadjuvant treatment setting (100% and 96%), antibiotic prophylaxis (40% and 43%), and chemotherapy (TAC [docetaxel, doxorubicin, cyclophosphamide] in 96% and 93%).
Higher Febrile Neutropenia Rate
The trial was terminated early due to higher than expected rates of febrile neutropenia in the G-CSF 1–2 group, with febrile neutropenia being observed in 10% of patients in the G-CSF 1–6 group vs 36% of those in the G-CSF 1–2 group; febrile neutropenia occurred in 24% of the latter group during the third chemotherapy cycle.
Total Costs and Incremental Cost-Effectiveness Ratio
Over all cycles, mean total costs were €20,658 per patient in the G-CSF 1–6 and €17,168 in the G-CSF 1–2, a mean additional cost of €3,491 per patient in the G-CSF 1–6 group. The incremental cost-effectiveness ratio of G-CSF 1–6 vs G-CSF 1–2 was €13,112 per patient with episodes of febrile neutropenia prevented. Chemotherapy and G-CSF costs accounted for 83% of total costs in the G-CSF 1–6 group and 78% in the G-CSF 1–2 group. Overall mean costs associated with chemotherapy were approximately €10,300 and did not differ significantly between the two groups. Mean costs of G-CSF prophylaxis were €5,171 per patient in the G-CSF 1–2 group vs €8,643 per patient in the G-CSF 1–6 group.
Febrile Neutropenia Costs
The mean febrile neutropenia–related costs per episode were €2,767 per patient in the G-CSF 1–6 group vs €1,786 in the G-CSF 1–2 group, with these costs primarily reflecting hospitalization costs. The mean duration of febrile neutropenia–related hospitalization was 5.8 days in the G-CSF 1–6 group vs 3.4 days in the G-CSF 1–2 group, with the mean duration of antibiotic treatment being comparable in both. The mean febrile neutropenia–related costs per patient were €395 in the G-CSF 1–6 group and €732 in the G-CSF 1–2 group.
Mean non–febrile neutropenia–related costs were €1,244 per patient in the G-CSF 1–6 group and €1,041 in the G-CSF 1–2 group. The primary reasons for hospitalization were fever and gastrointestinal complaints.
Likelihood of Cost-Effectiveness
Modeling of uncertainty surrounding the expected incremental costs and effects indicated that it is virtually certain that G-CSF 1–6 is both more effective and more costly than G-CSF 1–2. Estimation of probabilities that G-CSF 1–6 is cost-effective across a range of values for a patient with febrile neutropenia prevented showed that if this value is low (< €10,000), the probability that G-CSF 1–6 is considered cost-effective is low (< 20%); if the value is ≥ €40,000, there is a 100% probability that G-CSF 1–6 is cost-effective.
The investigators stated, “We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of [febrile neutropenia] prevented.”
The study was supported by sanofi-aventis Netherlands BV, a grant from the Netherlands Organization for Health Research and Development, and the Dutch Breast Cancer Trialists’ Group.
Vivianne C.G. Tjan-Heijnen, MD, PhD, of Maastricht University Medical Centre is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
