Dose-dose doxorubicin and cyclophosphamide (ddAC) is a treatment option for women with human epidermal growth factor receptor 2–negative (HER-2) breast cancer (BC). However, this regimen is associated with a high risk of neutropenia and febrile neutropenia (FN). To prevent and/or manage this complication, the use of granulocyte colony–stimulating factor (G-CSF) is recommended with each chemotherapy cycle.
Pegfilgrastim, which is the pegylated formulation of filgrastim, is widely used for this indication. However, it is advised that pegfilgrastim should not be administered within 24 hours after or 14 days prior to chemotherapy, thereby necessitating a return to the infusion center on the day following chemotherapy administration. If pegfilgrastim could be administered at the time of chemotherapy, this would improve convenience and possibly enhance adherence.
To examine the effects of same-day versus next-day pegfilgrastim administration, a retrospective, multicenter (three-site) cohort study was conducted that enrolled patients with BC aged 18 years or older who received ddAC between June 1, 2016, and May 31, 2020. Patients were eligible for inclusion if they had received an initial dose of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 for a total of four 14-day cycles. One site administered pegfilgrastim on the same day as chemotherapy, and two sites administered the G-CSF after chemotherapy. Exclusion criteria were if chemotherapy was received within 1 year prior to ddAC; if patients received less than four cycles of ddAC and pegfilgrastim was administered (unless the regimen was discontinued due to CIL); if patients received pegfilgrastim >48 hours after ddAC; if laboratories were drawn >48 hours prior to each chemotherapy cycle; or if patients received prophylactic antibiotics during treatment.
FN was defined as an absolute neutrophil count (ANC) <1,000 cells/mm3 and having a temperature of >100.4 degrees Fahrenheit or having a diagnosis of neutropenic fever. Neutropenia was defined as per the Common Terminology Criteria.
The primary endpoint was the difference in the incidence of FN between same-day versus next-day administration of pegfilgrastim, and the secondary endpoints included differences in rates of hospitalization, acute-care visits due to neutropenic complications, chemotherapy dose reduction or cycle delays, antibiotic use directly associated with CIL, and the presence of grade 3 or 4 neutropenia. An additional outcome was the evaluation of device failure rates in patients receiving pegfilgrastim via an on-body autoinjector.
A total of 300 patients were enrolled in the study, including 146 in the same-day pegfilgrastim regimen and 214 patients in the next-day pegfilgrastim regimen (mean age in both groups: 58 years). All except for one patient in the same-day pegfilgrastim dose received the same pegfilgrastim formulation throughout the four chemotherapy cycles, whereas 5.1% of the next-day CSF group received more than one pegfilgrastim formulation. Within the next-day G-CSF group, 155 received at least one dose via the autoinjector, with the majority of these patients (92.9%) receiving pegfilgrastim via autoinjector for all four cycles.
The authors found that same-day pegfilgrastim administrations was associated with a significantly increase rate of developing FN compared with next-day pegfilgrastim dosing (24.7% vs. 11.7%, P = .002). Also significantly increased with same-day dosing were the percentage of patients who developed other neutropenic complications, including acute-care visits (11.6% vs. 2.8%, P = .0016); grade 3 or 4 neutropenia (38.4% vs. 13.6%, P <.001); chemotherapy dose reductions (21.2% vs. 6.1%, P <.0001); and antibiotic use (26.7% vs. 12.6% P = .001). Further, pegfilgrastim autoinjector failure rate was 5.2% per patient, or 1.3% failure rate per cycle.
This study enforces current practice of next-day dosing of pegfilgrastim in patients with BC. It provides evidence for pharmacists to share with patients and providers regarding the risk of same-day pegfilgrastim administration following chemotherapy. It also highlights the need for close pharmacist monitoring for treatment failure in patients who are receiving pegfilgrastim via the autoinjector.
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