Same-Day Dosing of Eflapegrastim and Chemotherapy Is Safe, Reduces Duration of Severe Neutropenia in Early-Stage Breast Cancer

Administration of the granulocyte colony-stimulating factor (GCSF) eflapegrastim (Rolvedon) on the same day as cycle 1 of docetaxel and cyclophosphamide (TC) was effective, safe and produced comparable outcomes to those seen with next-day dosing schedules of eflapegrastim in patients with early-stage breast cancer, according to data from a phase 1 study (NCT04187898).1

Findings presented during the 42nd Annual Miami Breast Cancer Conference showed that, among 49 evaluable patients treated with TC and elfapegrastim on the same day, the mean time to absolute neutrophil count (ANC) recovery in cycle 1 was 1.8 days (SD, 1.1; range, 0-4). Notably, patients had a mean nadir at 1.8 x 109/L.

Moreover, among all efficacy-evaluable patients, only 1 patient experienced febrile neutropenia, and none reported neutropenic complications, defined as use of antibiotics and/or hospitalizations, during the study. The incidence of severe neutropenia was 42.9%; this was clinically defined as grade 4 neutropenia with ANC less than 0.5 x 109/L. The mean duration of severe neutropenia (DSN) was 0.7 (SD, 0.9; range, 0-3).

“While 43% of patients receiving TC experienced severe neutropenia, the mean duration of severe neutropenia following eflapegrastim [administration] was less than a day and no patients experienced febrile neutropenia–related complications, such as hospitalization or intervention with antibiotics,” lead study author Lee Schwartzberg, MD, and coauthors wrote in a poster presentation of the data. Schwartzberg is the chief of Medical Oncology and Hematology for Renown Health–William N. Pennington Cancer Institute and is a professor of clinical medicine at the University of Nevada–Reno.

Background and Study Design

In September 2022, eflapegrastim-xnst injection was approved by the FDA to decrease the incidence of infection caused by febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with clinically significant incidence of febrile neutropenia.2 Data from the phase 3 RECOVER (NCT02953340) and ADVANCE (NCT02643420) trials, which supported this approval, demonstrated the noninferiority of eflapegrastim vs pegfilgrastim (Neulasta) in managing severe neutropenia in this patient population.

This open-label, single-arm, phase 1 study was conducted across 13 sites in the United States.1 Patients included in the study were at least 18 years of age with newly-diagnosed early-stage breast cancer (defined as operable stage I to stage IIIA breast cancer and eligible for adjuvant or neoadjuvant TC); adequate hematological, renal, and hepatic function (defined as ANC ≥1.5 x 109/L; platelet count ≥100 x 109/L; hemoglobin ≥10 g/dL), creatinine clearance of greater than 50 mL/min, and a total bilirubin of 1.5 mg/dL or less, with an aspartate aminotransferase/alanine aminotransferase level of 2.5 x upper limit of normal or less; and an ECOG performance status of 0 to 2.

Upon enrollment, patients entered a screening period of 30 days before receiving intravenous docetaxel at 75 mg/m2 and cyclophosphamide at 600 mg/m2 on cycle day 1. After 30 minutes, patients received a subcutaneous, single, fixed dose of eflapegrastim at 13.2 mg (3.6 mg GCSF). Notably, patients were treated with the same dosing of eflapegrastim in cycles 2 to 4 of TC.

The primary end point was time to recovery of ANC from nadir to 1.5 x 109/L or greater in cycle 1; secondary end points included incidence of severe neutropenia (ANC <0.5 x 109/L) and febrile neutropenia (ANC <1.0x 109/L and temperature of >38.3 °C or 2 consecutive readings of ≥38.0 °C over 2 hours); DSN; the incidence of neutropenic complications, including the use of antibiotics and/or hospitalizations; and safety.

In the total study population (n = 53), the mean age was 62.7 years (range, 33-82), mean weight was 81.9 kg (range, 46.7-158.0), and all patients were female. Regarding race, patients were White (62.3%), Black (9.4%), Asian (7.5%), or other (20.8%). Patients had ECOG performance statuses of 0 (52.8%) or 1 (47.2%). The mean ANC (x 109/L) was 5.71 (SD, 2.9).

Additional Safety Data

All patients who received at least 1 dose of eflapegrastim (n = 53) were assessed. At least 1 treatment emergent adverse effect (TEAE) was experienced by 96.2% of patients, most of which were associated with chemotherapy. Eflapegrastim-related TEAEs occurred in 88.7% of patients, 11.3% of which were grade 3 or higher.

TEAEs of special interest, which comprised musculoskeletal AEs associated with GCSF class therapeutics, were reported by 81.1% of patients. The most common any-grade musculoskeletal TEAEs were bone pain (52.8%) and back pain (26.4%). Other TEAEs of special interest included pain in extremity (20.8%), arthralgia (17.0%), myalgia (13.2%), muscle spasms (9.4%), and muscular weakness (7.5%).

Eflapegrastim-related TEAEs of special interest included musculoskeletal pain (67.9%), bone pain (49.1%), back pain (20.8%), pain in extremity (15.1%), arthralgia (15.1%), myalgia (7.5%), muscle spasms (5.7%), and muscular weakness (1.9%). Grade 3 or higher musculoskeletal AEs associated with eflapegrastim occurred in 5 patients, and included bone pain (3.8%) back pain (3.8%), and pain in an extremity (1.9%).

Eflapegrastim-related pruritus and urticaria both occurred in 1 patient and led to required drug interruption; eflapegrastim-related dyspnea in 1 patient led to drug discontinuation. During the study, there were no deaths reported.

“No new safety concerns were seen, and the eflapegrastim-related AEs were consistent with those observed with other GCSF products,” the study authors noted.

References

1. Schwartzberg L, Marathe O, Chawla S, et al. Eflapegrastim, a long-acting GCSF, administered the same day as chemotherapy in patients with early-stage breast cancer: results from a multicenter, open-label, study. Presented at: 42nd Annual Miami Breast Cancer Conference; March 6-9, 2025; Miami Beach, FL. Poster 88.
2. Spectrum Pharmaceuticals receives FDA approval for Rolvedon™ (eflapegrastim-xnst) injection. News release. Spectrum Pharmaceuticals. September 9, 2022. Accessed March 8, 2025. https://bwnews.pr/3DayQAD