唑来膦酸非专利药或地诺单抗用于乳腺癌骨转移女性的成本效果分析
骨骼相关事件，如病理性骨折、脊髓压缩、骨转移所需放疗或手术，引起发病率增加、生活质量下降、医疗系统支出。2017年1月3日《美国医学会杂志》正式发表的大型随机研究（肿瘤临床研究联盟CALGB70604）结果表明，唑来膦酸每三个月与每月用药相比，减少骨骼相关事件的风险相似。每月地诺单抗（德尼单抗、狄诺塞麦）、每月或每三个月唑来膦酸（专利药或非专利药）的性价比尚不明确。
肿瘤临床研究联盟（Alliance）：由美国外科医师学会肿瘤学组（ACOSOG）、癌症与白血病协作组（CALGB）、北中地区癌症治疗协作组（NCCTG）于2014年合并而成。
2017年10月12日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表纽约西奈山伊坎医学院、梅奥医院、北卡罗来纳大学、海伦格雷厄姆癌症中心与研究所、国家癌症研究所与克里斯蒂安娜医疗集团社区肿瘤研究项目、密歇根大学的研究报告，对每三个月唑来膦酸、每月唑来膦酸、每月地诺单抗用于乳腺癌骨转移女性的成本效果进行比较。
该研究在CALGB70604研究的基础上，利用马尔可夫模型，计算三种治疗方案避免每例骨骼相关事件的成本，对地诺单抗与唑来膦酸减少骨骼相关事件发生率进行敏感性分析，同时计算质量校正寿命年，并从美国支付者角度进行分析。值得一提的是，该研究未由诺华或安进（分别为唑来膦酸、地诺单抗的专利药生产商）提供赞助。
结果发现：
地诺单抗与每三个月唑来膦酸非专利药相比平均成本高9倍。
三个治疗组的质量校正寿命年几乎相同，每三个月唑来膦酸的成本最低。
根据敏感性分析，地诺单抗与每三个月唑来膦酸相比，避免每例骨骼相关事件的增量成本范围：162918～347655美元。
因此，每三个月唑来膦酸与每月地诺单抗相比，减少骨骼相关事件的性价比较高。该分析为首个纳入唑来膦酸非专利药成本的成本效果分析之一，亦为首个不由专利药生产商赞助的独立成本效果分析之一。每三个月唑来膦酸是性价比较高的方案，并且可以合理地替代每月地诺单抗。
转移性乳腺癌女性使用唑来膦酸非专利药与联盟研究的成本效果分析讨论
Discussion on the Cost-Effectiveness Analysis of the CALGB/Alliance Trial and the Use of Zoledronic Acid Generic in Women With Metastatic Breast Cancer.
Dominique Levêque
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J Clin Oncol. 2017 Oct 12. [Epub ahead of print]
Cost-Effectiveness Analysis of Monthly Zoledronic Acid, Zoledronic Acid Every 3 Months, and Monthly Denosumab in Women With Breast Cancer and Skeletal Metastases: CALGB 70604 (Alliance).
Shapiro CL, Moriarty JP, Dusetzina S, Himelstein AL, Foster JC, Grubbs SS, Novotny PJ, Borah BJ.
Icahn School of Medicine, Mt Sinai, NY; Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN; University of North Carolina at Chapel Hill, Chapel Hill, NC; Helen F. Graham Cancer Center and Research Institute, Christiana Care NCI Community Oncology Research Program, Newark, DE; University of Michigan, Grand Rapids, MI.
PURPOSE: Skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, or the necessity for radiation or surgery to bone metastasis cause considerable morbidity, decrements in quality of life, and costs to the health care system. The results of a recent large randomized trial (Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases.
METHODS: Using a Markov model, costs per SRE avoided were calculated for the three treatments. Sensitivity analyses were performed where denosumab SRE probabilities were assumed to be 50%, 75%, and 90% lower than the ZA SRE probabilities. Quality-adjusted life-years were also calculated. The analysis was from the US payer perspective.
RESULTS: The mean costs of the denosumab treatment strategy are nine-fold higher than generic ZA every 3 months. Quality-adjusted life-years were virtually identical in all the three treatment arms; hence, the optimal treatment would be ZA every 3 months because it was the least costly treatment. The sensitivity analyses showed that relative to ZA every 3 months, the incremental costs per mean SRE avoided for denosumab ranged from $162,918 to $347,655.
CONCLUSION: ZA every 3 months was more CE in reducing the risks of SRE than monthly denosumab. This analysis was one of the first to incorporate the costs of generic ZA and one of the first independent CE analyses not sponsored by either Novartis or Amgen, the makers of ZA and denosumab, respectively. ZA every 3 months is the more CE option and more reasonable alternative to monthly denosumab.
PMID: 29023215
DOI: 10.1200/JCO.2017.73.7437