Regorafenib in Bone Sarcoma: A Systematic Review and Meta-Analysis of Its Effectiveness and Safety in Cancer Treatment

Abstract Objectives Bone sarcomas are aggressive malignancies with limited treatment options in advanced stages. Regorafenib, an oral multi-kinase inhibitor, has showed potential efficacy in early-phase trials. However, its overall effectiveness and safety profile in bone sarcoma remain unclear. This systematic review and meta-analysis aim to assess the clinical impact of regorafenib on survival outcomes and adverse events in patients with bone sarcomas. Methods A systematic search was conducted across PubMed, Web of Science, and Scopus for randomized controlled trials (RCTs) published between September 27, 2012, and April 2024. Eligible studies included full-text RCTs comparing regorafenib to placebo in the treatment of bone sarcomas. Meta-analyses, reviews, case reports, conference abstracts, ongoing trials, and animal studies were excluded from the analysis. The primary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Data synthesis was performed using a random-effects model, and heterogeneity was assessed via the I² statistic. The Cochrane Risk of Bias tool (RoB 2) was applied to evaluate study quality. Statistical analysis was conducted using R version 4.3.1. Results A total of five RCTs met the inclusion criteria. Regorafenib significantly improved PFS compared to placebo (MD = 9.69 weeks; 95% CI: 4.54, 14.84; I² = 0%), while no statistically significant improvement was observed in OS (MD = 0.85 weeks; 95% CI:-36.33, 38.02; I² = 0%). Predominantly observed treatment-emergent effects linked to regorafenib included hand-foot skin reaction, hypertension, asthenia or fatigue, and diarrhea. Conclusion Regorafenib significantly improves progression-free survival in bone sarcoma but does not show a clear benefit in overall survival. While adverse events are common, they are generally manageable. Further research is needed to optimize dosing, patient selection, and to determine the long-term survival benefits.