Assessing the Optimal Regimen: A Systematic Review and Network Meta-Analysis of the Efficacy and Safety of Long-Acting Granulocyte Colony-Stimulating Factors in Patients with Breast Cancer

SIMPLE SUMMARY: Patients with breast cancer undergoing chemotherapy are susceptible to prolonged and severe neutropenia. Multiple biosimilar long-acting granulocyte colony-stimulating factors (LA-G-CSFs) have been developed to treat chemotherapy-induced neutropenia. However, which LA-G-CSF is optimal remains inconclusive. Moreover, there is a lack of evidence supporting clinical decisions on LA-G-CSF dose escalation in poor conditions. This systematic review and network meta-analysis aimed to identify the most effective and safe LA-G-CSF regimen and explore the feasibility of dose escalation. Our findings reveal that certain LA-G-CSFs significantly outperform others (including the guideline-recommended pegfilgrastim 6 mg). An increased LA-G-CSF dosage might enhance efficacy without additional severe adverse events. Our research offers essential insights into precise drug selection and personalized dosing in preventing post-chemotherapy neutropenia. However, further high-quality investigations into the efficacy and safety of the use of LA-G-CSFs are warranted in the future. ABSTRACT: Patients with breast cancer undergoing chemotherapy are susceptible to prolonged and severe neutropenia. Multiple biosimilars of long-acting granulocyte colony-stimulating factors (LA-G-CSFs) have been newly developed to prevent this disease. Nonetheless, which LA-G-CSF regimen has the optimal balance of efficacy and safety remains controversial. Moreover, there is a lack of evidence supporting clinical decisions on LA-G-CSF dose escalation in poor conditions. PubMed, Embase, Cochrane Library, Web of Science, and several Chinese databases were searched (December 2022) to collect randomized controlled trials (RCTs) about LA-G-CSFs preventing chemotherapy-induced neutropenia in breast cancer patients. No restrictions were imposed on language. A Bayesian network meta-analysis was performed. We assessed the incidence of severe neutropenia (SN) and febrile neutropenia (FN), the duration of SN (DSN), and the absolute neutrophil account recovery time (ANCrt) for efficacy, while the incidence of severe adverse events (SAE) was assessed for safety. The study was registered in PROSPERO (CRD42022361606). A total of 33 RCTs were included. Our network meta-analysis demonstrated that lipegfilgrastim 6 mg and eflapegrastim 13.2 mg outperformed other LA-G-CSFs with high efficacy rates and few safety concerns (SUCRA of lipegfilgrastim 6 mg: ANC rt 95.2%, FN 97.4%; eflapegrastim 13.2 mg: FN 87%, SN 89.3%). Additionally, 3.6 mg, 4.5 mg, 6 mg, and 13.2 mg dosages all performed significantly better than 1.8 mg in reducing the duration of SN (3.6 mg: DSN, SMD −0.68 [−1.13, −0.22; moderate]; 4.5 mg: −0.87 [−1.57, −0.17; low]; 6 mg: −0.89 [−1.49, −0.29; moderate]; 13.2 mg: −1.02 [1.63, −0.41; high]). Increasing the dosage from the guideline-recommended 6 mg to 13.2 mg can reduce both the duration and incidence of SN (SMD −0.13 [−0.24 to −0.03], RR 0.65 [0.43 to 0.96], respectively), with no significant difference in SAE. For patients with breast cancer, lipegfilgrastim 6 mg and eflapegrastim 13.2 mg might be the most effective regimen among LA-G-CSFs. Higher doses of LA-G-CSF may enhance efficacy without causing additional SAEs.