Outcomes in Patients With Curative Malignancies Receiving Filgrastim as Primary Prophylaxis
Background: Granulocyte colony-stimulating factor prophylaxis has been shown to reduce the risk and duration of chemotherapy-induced neutropenia and febrile neutropenia and is recommended for at-risk patients receiving chemotherapy. Within the South Texas Veterans Health Care System, daily filgrastim injections remain the preferred formulation of granulocyte colony-stimulating factor for primary prophylaxis of febrile neutropenia.
Methods: This retrospective, single-center cohort study included 59 patients who received daily filgrastim as primary prophylaxis with a curative cancer diagnosis and a chemotherapy regimen at the South Texas Veterans Health Care System from September 1, 2015 to September 24, 2020. Patients had either a high risk for febrile neutropenia or a chemotherapy regimen with an intermediate risk for febrile neutropenia and additional risk factors. The primary outcome was the incidence of neutropenia/febrile neutropenia leading to treatment delays. Secondary outcomes included chemotherapy dose decreases or discontinuations, hospitalizations, days of hospitalization, infections, extended duration of filgrastim, and transitions to pegfilgrastim due to neutropenia/febrile neutropenia.
Results: Patients received a median (IQR) of 7 (5-10) doses of filgrastim for primary prophylaxis. Overall, 10 patients (17%) experienced treatment delays due to neutropenia/febrile neutropenia. Fifteen patients (25%) were hospitalized with a median (IQR) length of stay of 5 (4-7) days, 9 patients (15%) had documented infections, and 2 patients (3%) required a chemotherapy dose reduction. Additionally, 9 patients (15%) required an additional median (IQR) of 2 (2-5) doses of filgrastim, and 9 (15%) patients were transitioned to pegfilgrastim.
Conclusions: These results suggest that additional measures such as tracking postnadir absolute neutrophil counts should be performed to ensure patients receive an appropriate number of filgrastim doses to prevent complications associated with neutropenia/febrile neutropenia.
Real-world data are limited regarding G-CSF practice patterns; however, available data demonstrate patients may receive suboptimal treatment courses of filgrastim leading to increased complications associated with neutropenia and FN, such as dose delays and hospitalizations.8,9 At the South Texas Veterans Health Care System, 48 patients (81%) received a filgrastim course of ≥ 7 days as an initial course for primary prophylaxis. Multivariate analyses performed by Weycker and colleagues described a decreased risk of hospitalization for neutropenia or FN with each additional day of filgrastim prophylaxis; however, such analysis could not be performed in our data set due to the small sample size.8 In this review, 10 patients (17%) experienced treatment delays due to neutropenia or FN, mirroring previously published data. The hospitalization rate of 25% is higher than the published incidence of 5.2% of cancer-related hospitalizations among adults.7,10 This difference may be explained by a difference in health care access for the veteran population.
As an alternative to daily filgrastim injections, the National Comprehensive Cancer Network also recommends a single dose of pegfilgrastim for primary prevention of FN. Efficacy benefits of pegfilgrastim use include increased patient adherence due to a single injection, a reduction in FN incidence and FN-related hospitalizations, and improved time to ANC recovery compared with filgrastim.11 There are reports suggesting pegfilgrastim significantly reduces neutropenia and FN incidence to a greater extent compared with daily filgrastim injections.6 In patients with breast cancer receiving dose-dense adjuvant chemotherapy, there are data demonstrating that patients who received filgrastim were more likely to experience severe neutropenia, dose reductions, and treatment delays leading to lower dose density compared with pegfilgrastim.12 Of the 19 patients with breast cancer included in our population, 26% experienced one of the previously described outcomes leading to either extensions of daily filgrastim injections or transitions to pegfilgrastim to successfully maintain dose density. In patients with acute myeloid leukemia receiving consolidation chemotherapy, filgrastim was found to be associated with a statistically significant increased risk of hospitalizations compared with pegfilgrastim.13 The one patient with acute myeloid leukemia included in our study did not require additional hospitalizations for neutropenia or FN after transitioning to pegfilgrastim.
Given the cost advantage, the South Texas Veterans Health Care System continues to prefer daily filgrastim injections. A recent survey demonstrated that 73% of patients at 23 sites in the Veterans Health Administration used filgrastim rather than pegfilgrastim for cost savings, although it is recognized that daily filgrastim injections are less convenient for patients.14 This analysis did not review costs associated with hospitalization for FN or the appropriateness of G-CSF use. Cancer-related neutropenia accounts for 8.3% of all cancer-related hospitalization costs among adults; the average hospitalization costs nearly $25,000 per stay and about $2.3 billion among adult patients with cancer annually.10,15
Limitations
This study has limitations that affected the applicability and interpretation of the results. This included the study design since it was a retrospective, single-center, descriptive cohort study. Patient adherence to daily filgrastim injections could not be assessed due to the retrospective nature of the study. The small sample size of 59 patients was prohibitive for utilization of additional analytical tools. Additionally, the predominately male veteran population may make applicability to non-VA populations restrictive.
