地诺单抗与唑来膦酸治疗恶性肿瘤伴骨转移安全性和有效性的Meta分析

Efficacy and safety of denosumab versus zoledronic acid in treatment of bone metastasis:a meta-analysis

目的系统评价地诺单抗与唑来膦酸治疗恶性肿瘤伴骨转移的有效性和安全性。方法利用Cochrane library、Pub Med、OVID、Springer Linker、Science Direct、EBSCO等数据库检索文献,按Cochrane风险偏倚评估工具评价纳入文献质量并提取文献数据,应用Rev Man 5.3软件进行Meta分析。结果纳入4项临床随机对照试验,共6 029例患者,包含7篇相关文献。Meta分析结果显示,与唑来膦酸比较,地诺单抗能明显延缓骨相关事件(SREs)发生的时间,降低骨转移标志物Ⅰ型胶原交联氨基末端肽/肌酐(uNTx/Cr)、骨源性碱性磷酸酶(S-BALP)浓度,预防骨放疗,延缓疼痛加剧和干预,同时治疗后贫血、急性期反应和肾毒性的发生率更低,差异均有统计学意义(均P<0.01);两组患者总生存(OS)时间、疾病进展时间、预防病理性骨折、预防骨手术、预防脊髓压迫、不良事件(AEs,包括恶心、疲劳、背痛、下颌骨坏死等)的发生率等指标比较,差异均无统计学意义(均P>0.05)。结论地诺单抗在临床有效性和安全性方面优于唑来膦酸,为恶性实体瘤伴骨转移患者的临床预防与治疗提供了新的方案。

Objective To evaluate the effectiveness and safety of denosumab versus zoledronic acid in treatment of bone metastasis in cancer patients. Methods Clinical studies of denosumab and zoledronic acid in treating bone metastasis were searched from Cochrane Library, PubMed, OVID, Springer Linker, Science Direct, EBSCO and other databases. The quality of literature were evaluated with Cochrane risk of bias assessment tools. The meta-analysis was performed with software Rev Man 5.3. Results Four RCTs reported in 7 papers and involving 6029 patients were included in the meta-analysis. Meta-analysis showed that denosumab was superior to zoledronic acid in delaying the time to skeleton-related events （SREs）, decreasing the concentration of bone metastasis markers uNTx/Cr and S-BALP, prolonging the time to radiotherapy, reducing the pain severity and pain interference. The denosumab group had lower incidence rate of anemia, acute phase reactions and renal toxicity. There were no significant differences in overall survival, disease progression, pathologic fractures, surgery to bone, spinal cord compression and incidence rates of nausea, fatigue, back pain, osteonecrosis of the jaw between two groups. Conclusion Denosumab is superior to zoledronic acid in clinical efficacy and safety for treatment of bone metastasis in cancer patients.