Efficacy and safety analysis of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in the treatment of osteosarcoma: a systematic review and meta-analysis

Osteosarcoma is a rare and aggressive bone cancer, with targeted therapy using VEGFR-TKIs (Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors) emerging as a promising treatment option. This meta-analysis evaluated the efficacy and safety of VEGFR-TKIs in osteosarcoma treatment, analyzing studies from PubMed, Embase, Web of Science, and Cochrane databases until 18 September 2023, involving 14 trials with 447 patients. Results indicated that monotherapy with VEGFR-TKIs had an objective response rate(ORR) of 16% (95% CI = 9–24%) and a disease control rate(DCR) of 65% (95% CI = 57–73%). The average progression-free survival(PFS) was 4.27 months(95% CI = 3.21–5.34), with overall survival(OS) at 9.26 months(95% CI = 7.75–10.77). Combined treatments led to an ORR of 7% (95% CI = 2–12%) and a DCR of 71% (95% CI = 54–88%), with PFS of 5.62 months(95% CI = 3.57–7.74) and OS of 11.84 months(95% CI = 9.26–14.43). Treatment-related adverse events occurred in 83% (95% CI = 74–92%), with severe events in 32% (95% CI = 3–61%). In conclusion, VEGFR-TKIs demonstrate effectiveness and tolerability in osteosarcoma treatment, providing significant disease control and survival advantages despite notable adverse event risks. PROSPERO (CRD42024579648)骨肉瘤（Osteosarcoma）是一种罕见且侵袭性极强的骨恶性肿瘤，以VEGFR-TKIs（血管内皮生长因子受体酪氨酸激酶抑制剂，Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors）为代表的靶向治疗正成为其颇具前景的治疗选择。本荟萃分析评估了VEGFR-TKIs用于骨肉瘤治疗的有效性与安全性，检索了截至2023年9月18日发表于PubMed、Embase、Web of Science及Cochrane数据库的相关研究，共纳入14项试验、447例患者。结果显示，VEGFR-TKIs单药治疗的客观缓解率（ORR，Objective Response Rate）为16%（95%CI：9%~24%），疾病控制率（DCR，Disease Control Rate）为65%（95%CI：57%~73%）；平均无进展生存期（PFS，Progression-Free Survival）为4.27个月（95%CI：3.21~5.34），总生存期（OS，Overall Survival）为9.26个月（95%CI：7.75~10.77）。联合治疗方案的客观缓解率为7%（95%CI：2%~12%），疾病控制率为71%（95%CI：54%~88%），无进展生存期为5.62个月（95%CI：3.57~7.74），总生存期为11.84个月（95%CI：9.26~14.43）。治疗相关不良事件发生率为83%（95%CI：74%~92%），其中严重不良事件发生率为32%（95%CI：3%~61%）。综上，VEGFR-TKIs在骨肉瘤治疗中展现出有效性与良好耐受性，尽管存在显著的不良事件风险，但可带来显著的疾病控制与生存获益。本研究已在PROSPERO注册库（CRD42024579648）完成注册。