Abstract PS1-05-02: Efbemalenograstim alfa significantly reduces incidence of incidence of severe chemotherapy-induced neutropenia in later cycles: Results of a meta analysis

Abstract Introduction: Efbemalenograstim alfa, a non-PEGylated, long-acting, human granulocyte-colony stimulating factor was recently evaluated for the management of chemotherapy-induced neutropenia in a phase III trial of 393 patients with stage I-III invasive breast cancer. The study met the primary end point, demonstrating that a single dose of efbemalenograstim alfa was noninferior to pegfilgrastim, decreasing the duration of severe neutropenia in cycle 1. An additional endpoint of the phase III trial was the incidence of severe neutropenia (ISN; grade 4, ANC 0.5 × 109/L) across all chemotherapy cycles, which demonstrated significant reductions in ISN at later cycles. Here, we aimed to investigate is these reductions in ISN in later chemotherapy cycles occurred in previous trials of efbemalenograstim alfa and with different chemotherapy regimens. Methods: ISN rates from four cycles from phase III trials of efbemalenograstim alfa and three different chemotherapy regimens, docetaxel + cyclophosphamide (TC) (Trial 1), epirubicin + cyclophosphamide (EC) (Trial 2), and high myelotoxic docetaxel + doxorubicin (TA) (Trial 3 + historic pegfilgrastim and filgrastim comparative data) were evaluated. Results: Trial 1 included 197 patients randomized to efbemalenograstim alfa, compared to 196 randomized to pegfilgrastim that received TC chemotherapy. During cycle 1, ISN for both groups was 11.7%, but for subsequent cycles, ISN was lower for patients that received efbemalenograstim alfa compared to pegfilgrastim, 4.6% vs 5.1% for cycle 2, 2.6% vs 6.3% for cycle 3 (p=0.08) and significantly lower, 1.6% vs 5.3% for cycle 4 (p=0.05), respectively. Trial 2 included 122 patients randomized to efbemalenograstim alfa, compared to 120 randomized to filgrastim that received EC chemotherapy. During cycle 1, ISN was 14.2% for the efbemalenograstim alfa, compared to 16.0% for the filgrastim groups, with subsequent cycles at 1.7% vs 0.9%, respectively, for cycle 2, significantly lower, 0% vs 3.9% for cycle 3 (p=0.048) and 1.8% vs 4.0% for cycle 4. Trial 3 included 83 patients randomized to efbemalenograstim alfa and 39 randomized to placebo, therefore ISN for the TA chemotherapy regimen was compared to a historic pegfilgrastim + TA and filgrastim + TA phase III trial data, which showed an ISN at cycle 1 of 69.9% for efbemalenograstim alfa and 77-84% for pegfilgrastim, and 79-83% for filgrastim. ISN at cycle 2 was 15% for efbemalenograstim alfa and much higher for pegfilgrastim 45-57% and filgrastim 54-55%, and similarly for cycle 3, 20%, 37-56% and 53-60% and cycle 4, 10%, 45-51% and 49-55%, respectively. Conclusion: Across studies, non-PEGylated efbemalenograstim alfa has demonstrated equivalent or lower incidence rates of severe neutropenia (grade 4, ANC 0.5 × 109/L) during the first cycle of three types of chemotherapy (TC, EC and TA) and importantly, significantly lower rates in later cycles when compared to pegfilgrastim and filgrastim. These findings demonstrate that efbemalenograstim alfa may be more effective at preventing severe, life-threatening neutropenia at later chemotherapy cycles, which has meaningful implications for real-world breast cancer patients that are likely to receive chemotherapy for longer durations. Citation Format: J. A. Glasby. Efbemalenograstim alfa significantly reduces incidence of incidence of severe chemotherapy-induced neutropenia in later cycles: Results of a meta analysis abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-05-02.