Efficacy and safety of mecapegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer: a randomized, multicenter, active-controlled phase III trial

Background: Neutropenia is a common complication from chemotherapy. Mecapegfilgramtim (code name HHPG-19K), a long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF), has been developed. This study was to evaluate the efficacy and safety of mecapegfilgrastim for reducing neutropenia compared with filgrastim. Methods: This was a randomized, controlled non-inferiority study. A total of 339 breast cancer patients who were eligible for (neo) adjuvant chemotherapy were randomized assigned into three groups to receive mecapegfilgrastim 100 μg/kg, mecapegfilgrastim fixed dose of 6 mg or filgrastim 5 μg/kg/day in the first cycle of chemotherapy. The primary endpoint was the duration of grade ≥3 neutropenia in cycle 1. The secondary endpoints included the duration of grade ≥3 neutropenia in cycles 2–4, incidence of grade ≥3 neutropenia, and febrile neutropenia (FN). The safety profile was also evaluated. Results: The mean duration of grade ≥3 neutropenia was 1.06 [95% confidence interval (CI): 0.65, 1.26] days in mecapegfilgrastim 100 μg/kg group, 1.23 (95% CI: 0.84, 1.88) days in mecapegfilgrastim 6 mg group, and 2.06 (95% CI: 1.66, 2.46) days in the filgrastim group. The mean difference between mecapegfilgrastim 100 μg/kg and filgrastim was –1.00 (95% CI: –1.52, –0.48), the mean difference between mecapegfilgrastim 6 mg and filgrastim was –0.83 (95% CI: –1.36, –0.30). The upper bounds of 95% CI for the difference between mecapegfilgrastim and filgrastim were all Conclusions: Long-acting mecapegfilgrastim (100 μg/kg and fixed 6 mg) is very effective and well tolerated when administered in the primary prophylaxis of chemotherapy induced neutropenia and in consecutive-cycle treatment. In some clinical parameters, mecafilgrastim is non-inferior and even superior to filgrastim. The fixed 6 mg-dose regimen showed similar efficacy and safety profile compared with 100 μg/kg regimen, and would be the preference in clinical practice, due to the convenient once-per-cycle administration and high-degree treatment compliance for the patients. This study provided new evidence for the novel long-acting rhG-CSF, mecapegfilgrastim, which would be a new alternative for clinical practice for prophylaxis of chemotherapy induced neutropenia.