Safety and Efficacy of Filgrastim in the Prevention of Chemotherapy-Induced Neutropenia: A PRISMA 2020-Compliant Systematic Review and Meta-Analysis

Background: Chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) represent the most prevalent and clinically consequential dose-limiting toxicities of myelosuppressive cancer therapy. Filgrastim (recombinant human granulocyte colony-stimulating factor; rhG-CSF) has been used as primary and secondary prophylaxis of CIN for more than three decades, yet pooled effect estimates and heterogeneity quantification from the full body of randomized evidence have not been formally synthesized under PRISMA 2020 standards. Objectives: To systematically review and meta-analyse randomized controlled trials (RCTs) evaluating filgrastim versus placebo or no treatment for the prevention of CIN in adult cancer patients receiving cytotoxic chemotherapy, with primary focus on FN incidence and pre-specified secondary outcomes. Eligibility Criteria: RCTs in adult patients with non-myeloid malignancies receiving filgrastim 5 mcg/kg/day SC/IV versus placebo or no treatment, reporting FN or grade 3/4 neutropenia outcomes. Non-English publications and paediatric trials (<18 years) were excluded. Information Sources: PubMed/MEDLINE (1991–2025), EMBASE, Cochrane CENTRAL, ClinicalTrials.gov, WHO ICTRP, and reference lists of eligible studies and prior systematic reviews. Risk of Bias: Assessed using the Cochrane Risk of Bias tool version 2 (RoB 2) for RCTs. Certainty of evidence evaluated using GRADE methodology. Synthesis: Random-effects meta-analysis using the Der Simonian-Laird method. Summary relative risk (RR) with 95% confidence intervals (CI), Cochran Q-test for heterogeneity, I² statistic, tau² for between-study variance. Funnel plot asymmetry assessed by Egger’s test. Results: Eleven RCTs (n=2,553 patients) met eligibility for the primary analysis. Filgrastim significantly reduced FN incidence versus placebo/no treatment (pooled RR 0.58; 95% CI 0.50–0.67; I²=35.4%; Q=17.0; p=0.11), corresponding to a 42% relative risk reduction and a number needed to treat (NNT) of 5.3. Grade 3/4 neutropenia was also significantly reduced (RR 0.50; 95% CI 0.37–0.68; I²=48.2%). Duration of severe neutropenia was shortened by a mean of 3.8 days (95% CI 2.9–4.7). Bone pain occurred more frequently with filgrastim (RR 2.61; 95% CI 1.29–5.27). No statistically significant increase in serious adverse events was observed. Certainty of evidence: HIGH for FN incidence; MODERATE for grade 3/4 neutropenia and bone pain. No significant publication bias detected (Egger p=0.18). Conclusions: This PRISMA 2020-compliant meta-analysis provides high-certainty evidence that filgrastim substantially and significantly reduces FN incidence in adult cancer patients receiving myelosuppressive chemotherapy. The safety profile is acceptable. These findings support guideline-concordant use and the equivalence of biosimilar formulations. Registration: PROSPERO CRD420250643093.