Efbemalenograstim alfa as prophylaxis for chemotherapy-induced neutropenia in patients with non-small-cell lung cancer: a randomized, multicenter, phase II trial.

OBJECTIVE: Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended for patients receiving chemotherapy with a high risk of febrile neutropenia (FN), but its use remains suboptimal in patients receiving intermediate-risk regimens who have additional risk factors, for whom secondary prophylaxis (SPx) is commonly used despite limited prospective evidence comparing the two approaches. This study evaluated efbemalenograstim alfa (EFBGα), a novel Fc fusion G-CSF, as primary or secondary prophylaxis for chemotherapy-induced neutropenia (CIN) in patients with non-small-cell lung cancer (NSCLC) receiving intermediate-risk FN regimens who have additional risk factors. METHODS: This multicenter, randomized phase II trial enrolled chemotherapy-naïve patients with stage IIIB/IV NSCLC scheduled for platinum-taxane chemotherapy. Patients were randomized 2:1 to either primary prophylaxis (EFBGα 20 mg at 48 ± 4 h after each cycle) or secondary prophylaxis (given only after grade 3-4 neutropenia). The primary endpoint was the cycle 1 incidence of grade 3-4 neutropenia. RESULTS: A total of 102 patients were enrolled between February 2024 and December 2025, of whom 96 were included in the analysis: 63 in the primary prophylaxis group and 33 in the secondary prophylaxis group. In cycle 1, the incidence of grade 3-4 neutropenia was lower with primary prophylaxis than with secondary prophylaxis [20.6%, 95% confidence interval (CI) 11.5%-32.7% vs. 57.6%, 95% CI 39.2%-74.5%; risk difference -36.9%, 95% CI -52.4% to -16.1%; P < 0.001]. The median duration of grade 3-4 neutropenia was comparable between the groups (P = 0.144). Cycle 1 FN incidence was 1.6% in the primary and 6.1% in the secondary prophylaxis group. Treatment-related adverse events were mostly grade 1-2, with pain-related events (7.0%) being the most common. CONCLUSIONS: EFBGα exhibited promising efficacy and tolerability for CIN prophylaxis in patients with NSCLC and additional risk factors who are receiving intermediate-risk chemotherapy (IRC). The results support its use in both primary and secondary prophylactic strategies, and earlier initiation was associated with better CIN control.