Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
Health Technol Assess. 2013 Jul;17(29):1-386. doi: 10.3310/hta17290.
Denosumab offers an alternative, or additional, treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours.
The aim of this review was to assess the clinical effectiveness and cost-effectiveness of denosumab, within its licensed indication, for the prevention of SREs in patients with bone metastases from solid tumours.
Databases searched were MEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), The Cochrane Library (all sections; Issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011).
Only randomised controlled trials (RCTs) assessing denosumab, bisphosphonates (BPs) or best supportive care (BSC) in patients with bone metastases were included. Systematic reviews and observational studies were used for safety and quality-of-life assessments. Study quality was assessed using the Cochrane risk of bias tool. Studies suitable for meta-analysis were synthesised using network meta-analysis (NMA). A systematic review was conducted for cost, quality-of-life and cost-effectiveness studies. The results of this informed the cost-utility modelling. This principally estimated the cost-effectiveness of denosumab relative to zoledronic acid for when BPs are currently recommended and relative to BSC when BPs are not recommended or are contraindicated.
A literature search identified 39 studies (eight suitable for NMA). Denosumab was effective in delaying time to first SRE and reducing the risk of multiple SREs compared with zoledronic acid. Generally speaking, denosumab was similar to zoledronic acid for quality of life, pain, overall survival and safety. The NMA demonstrated that denosumab was more effective in delaying SREs than placebo, but was limited by numerous uncertainties. Cost-utility modelling results for denosumab relative to zoledronic acid were driven by the availability of the patient access scheme (PAS) for denosumab. Without this, denosumab was not estimated to be cost-effective compared with zoledronic acid. With it, the cost-effectiveness ranged between dominance for breast and prostate cancer, to between £5400 and £15,300 per quality-adjusted life-year (QALY) for other solid tumours (OSTs) including non-small cell lung cancer (NSCLC) and £12,700 per QALY for NSCLC. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price. Denosumab was not estimated to be cost-effective compared with BSC.
Only subgroup data were available for denosumab for NSCLC, and OSTs excluding NSCLC. The NMA was subject to numerous uncertainties. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price.
Denosumab, compared with zoledronic acid and placebo, is effective in delaying SREs, but is similar with regard to quality of life and pain. Cost-effectiveness showed that without the PAS denosumab was not estimated to be cost-effective relative to either zoledronic acid or BSC. With the PAS, denosumab was estimated to be cost-effective relative to zoledronic acid but not BSC.
PROSPERO number CRD42011001418.
The National Institute for Health Research Health Technology Assessment programme.
地舒单抗为预防实体瘤骨转移患者的骨骼相关事件（SREs）提供了一种替代或附加的治疗方法。
本研究旨在评估地舒单抗在其许可适应证内，预防实体瘤骨转移患者 SREs 的临床疗效和成本效益。
检索了 MEDLINE（1948 年至 2011 年 4 月）、EMBASE（1980 年至 2011 年 3 月）、Cochrane 图书馆（所有部分；2011 年第 1 期）和 Web of Science with Conference Proceedings（1970 年至 2011 年 5 月）。
仅纳入评估地舒单抗、双膦酸盐（BPs）或最佳支持治疗（BSC）在骨转移患者中的随机对照试验（RCTs）。系统评价和观察性研究用于评估安全性和生活质量。使用 Cochrane 偏倚风险工具评估研究质量。适合荟萃分析的研究使用网络荟萃分析（NMA）进行综合分析。对成本、生活质量和成本效益研究进行了系统评价。这为成本效用建模提供了信息。这主要估计了地舒单抗相对于唑来膦酸的成本效益，当目前推荐使用 BPs 时，以及当不推荐或禁忌使用 BPs 时相对于 BSC 的成本效益。
文献检索确定了 39 项研究（8 项适合 NMA）。与唑来膦酸相比，地舒单抗能有效延迟首次 SRE 的时间，并降低发生多次 SRE 的风险。一般来说，地舒单抗在生活质量、疼痛、总生存和安全性方面与唑来膦酸相似。NMA 表明，地舒单抗在延迟 SRE 方面比安慰剂更有效，但存在许多不确定性的限制。与唑来膦酸相比，地舒单抗的成本效用模型结果主要受地舒单抗患者准入方案（PAS）的影响。如果没有这个方案，与唑来膦酸相比，地舒单抗预计不会具有成本效益。有了这个方案，成本效益范围从乳腺癌和前列腺癌的优势，到其他实体瘤（OSTs），包括非小细胞肺癌（NSCLC）的 5400 英镑至 15300 英镑/质量调整生命年（QALY），以及 NSCLC 的 12700 英镑/QALY。由于估计患者获益较小，地舒单抗的成本效益对唑来膦酸的价格非常敏感。与 BSC 相比，地舒单抗预计不会具有成本效益。
仅可获得地舒单抗治疗 NSCLC 和 NSCLC 除外的 OST 的亚组数据。NMA 存在许多不确定性。由于估计患者获益较小，地舒单抗的成本效益对唑来膦酸的价格非常敏感。
与唑来膦酸和安慰剂相比，地舒单抗能有效延迟 SREs，但在生活质量和疼痛方面与唑来膦酸相似。成本效益表明，如果没有 PAS，与唑来膦酸或 BSC 相比，地舒单抗预计不具有成本效益。有了 PAS，与唑来膦酸相比，地舒单抗具有成本效益，但与 BSC 相比则没有。
PROSPERO 编号 CRD42011001418。
英国国家卫生研究院卫生技术评估计划。
