Comparative efficacy and safety of four long-acting granulocyte colony-stimulating factors for primary prophylaxis in patients with breast cancer: a prospective observational cohort study in China

Background: Long-acting granulocyte colony-stimulating factors (G-CSFs) are the standard of care for primary prophylaxis against chemotherapy-induced neutropenia in breast cancer, but comparative data remain limited. Methods: This prospective observational cohort study was conducted at a single center in Shanghai, China. Patients with breast cancer scheduled for high-febrile-neutropenia-risk chemotherapy and planned for long-acting G-CSF primary prophylaxis were eligible. Patients received subcutaneous pegfilgrastim, mecapegfilgrastim, telpegfilgrastim, or efbemalenograstim alfa once per cycle per clinical practice. The primary outcome was the incidence of grade 3/4 neutropenia (leukopenia), assessed during chemotherapy cycles and at follow-up visits. Safety was assessed via bone pain-related treatment-emergent adverse events (BPR TEAEs). Findings: Between March 25 and September 30, 2025, 407 patients were analyzed. Grade 3/4 neutropenia (leukopenia) occurred in 24.1%, varying numerically across agents (telpegfilgrastim 30.2%, mecapegfilgrastim 16.4%; overall P = 0.061). After multivariable adjustment, telpegfilgrastim was associated with a higher risk of grade 3/4 neutropenia (leukopenia) versus mecapegfilgrastim (OR = 2.46, P = 0.011). BPR TEAEs occurred in 62.4%, with similar incidence across groups (P = 0.32). Lower BPR TEAE risk was associated with ddEC chemotherapy (OR = 0.32, P = 0.0010) and postmenopausal status (OR = 0.53, P = 0.031). In exploratory analyses, administration at 24-48 h (versus <24 h) was associated with lower grade 4 neutropenia (leukopenia) (9.9% versus 27.3%, P = 0.011) and severe BPR TEAEs (0.5% versus 4.5%, P = 0.032), and a 3 mg pegfilgrastim dose was associated with comparable myeloprotection to 6 mg (29.4% versus 26.5%, P = 0.81) but fewer BPR TEAEs (29.4% versus 60.3%, P = 0.022). Interpretation: All four long-acting G-CSFs demonstrated clinical efficacy. Numerical variations and adjusted analyses indicated distinct clinical profiles, supporting tailored prophylaxis. Optimizing administration timing and considering dose reduction could improve benefit-risk balance. Larger prospective studies are needed to confirm these exploratory findings. Funding: None.