Abstract
OBJECTIVES: Bone sarcomas are rare, aggressive tumors with poor outcomes and limited systemic options in advanced stages. This systematic review and meta-analysis evaluated its efficacy and safety in bone sarcomas using randomized controlled trials (RCTs). METHODS: We searched PubMed, Scopus, and Web of Science for RCTs published from September 27, 2012, to October 14, 2024. After removing duplicates, 350 records were screened, and five RCTs met the inclusion criteria. Primary outcomes were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Study quality was assessed using the Cochrane Risk of Bias 2 (RoB2) tool. Meta-analyses were performed with a random-effects model, and heterogeneity was evaluated using I² statistics. All analyses were conducted using R version 4.3.1. RESULTS: A total of 350 records were screened after duplicate removal, of which 339 were excluded based on title and abstract. Eleven full-text articles were assessed for eligibility, and six were excluded for not meeting RCT criteria, resulting in five RCTs being included. Most had metastatic disease at baseline. Regorafenib significantly improved PFS (MD = 9.69 weeks; 95% CI: 4.54-14.84; I² = 0%), with no statistically significant overall survival (OS) benefit (MD = 0.85 weeks; 95% CI: -36.33 to 38.02; I² = 0%). These findings were consistent across studies and histological subtypes. All pooled analyses demonstrated zero or near-zero heterogeneity (I² = 0%), indicating highly consistent treatment effects among trials. No significant between-group heterogeneity was observed in subgroup analyses, confirming that regorafenib's benefit on progression-free survival was stable across different bone sarcoma types. Common regorafenib-related AEs included hand-foot skin reaction, hypertension, fatigue, and diarrhea. Grade 3-5 events were mostly hypertension and pain, generally manageable with dose modifications. Safety results were also consistent across studies, showing zero or near-zero heterogeneity (I² = 0%) and no significant subgroup differences, indicating a homogeneous safety profile across sarcoma subtypes. CONCLUSION: Regorafenib significantly improves progression-free survival in bone sarcomas across multiple subtypes, with a manageable toxicity profile. These results support its use as a novel therapy and highlight the need for future trials focused on optimizing dosing and patient selection. .