Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer by Age and Hormone Receptor Status: A Cost-Utility Analysis.
根据年龄和激素受体状态辅助曲妥珠单抗 HER2-Positive 早期乳腺癌: 一项成本-效用分析。

摘要

The anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab improves outcomes in patients with node-positive HER2+ early breast cancer. Given trastuzumab's high cost, we aimed to estimate its cost-effectiveness by heterogeneity in age and estrogen receptor (ER) and progesterone receptor (PR) status, which has previously been unexplored, to assist prioritisation.A cost-utility analysis was performed using a Markov macro-simulation model, with a lifetime horizon, comparing a 12-mo regimen of trastuzumab with chemotherapy alone using the latest (2014) effectiveness measures from landmark randomised trials. A New Zealand (NZ) health system perspective was adopted, employing high-quality national administrative data. Incremental quality-adjusted life-years for trastuzumab versus chemotherapy alone are two times higher (2.33 times for the age group 50-54 y; 95% CI 2.29-2.37) for the worst prognosis (ER-/PR-) subtype compared to the best prognosis (ER+/PR+) subtype, causing incremental cost-effectiveness ratios (ICERs) for the former to be less than half those of the latter for the age groups from 25-29 to 90-94 y (0.44 times for the age group 50-54 y; 95% CI 0.43-0.45). If we were to strictly apply an arbitrary cost-effectiveness threshold equal to the NZ gross domestic product per capita (2011 purchasing power parity [PPP]-adjusted: US$30,300; €23,700; £21,200), our study suggests that trastuzumab (2011 PPP-adjusted US$45,400/€35,900/£21,900 for 1 y at formulary prices) may not be cost-effective for ER+ (which are 61% of all) node-positive HER2+ early breast cancer patients but cost-effective for ER-/PR- subtypes (37% of all cases) to age 69 y. Market entry of trastuzumab biosimilars will likely reduce the ICER to below this threshold for premenopausal ER+/PR- cancer but not for ER+/PR+ cancer. Sensitivity analysis using the best-case effectiveness measure for ER+ cancer had the same result. A key limitation was a lack of treatment-effect data by hormone receptor subtype. Heterogeneity was restricted to age and hormone receptor status; tumour size/grade heterogeneity could be explored in future work.This study highlights how cost-effectiveness can vary greatly by heterogeneity in age and hormone receptor subtype. Resource allocation and licensing of subsidised therapies such as trastuzumab should consider demographic and clinical heterogeneity; there is currently a profound disconnect between how funding decisions are made (largely agnostic to heterogeneity) and the principles of personalised medicine.

译文

抗人表皮生长因子受体 2 (HER2) 单克隆抗体曲妥珠单抗改善淋巴结阳性 HER2 早期乳腺癌患者的预后。鉴于曲妥珠单抗的高成本,我们旨在通过年龄和雌激素受体 (ER) 和孕激素受体 (PR) 状态的异质性来估计其成本效益,这在以前是未被探索过的, 协助确定优先次序。使用马尔可夫宏观模拟模型进行成本效用分析,使用寿命范围,使用里程碑式随机试验的最新 (2014) 有效性指标比较曲妥珠单抗的 12 个月方案与单独化疗。采用了新西兰卫生系统的观点,采用了高质量的国家行政数据。曲妥珠单抗与单独化疗的增量质量调整生命年高出两倍 (50-54 岁年龄组的 2.33 倍; 95% CI 2.29-2.37) 对于最坏的预后 (ER-/PR-) 亚型与最好的预后 (ER/PR) 亚型相比,导致增加的成本效益比 (ICERs)对于 25-29 岁至 90-94 岁的年龄组,前者少于后者的一半 (50-54 岁年龄组的 0.44 倍; 95% CI 0.43-0.45)。如果我们要严格应用一个等于新西兰人均国内生产总值的任意成本效益阈值 (2011 购买力平价 [PPP]-调整: 30,300 美元; 23,700 欧元; 21,200 英镑),我们的研究表明曲妥珠单抗 (2011 PPP 调整后的 45,400 美元/35,900 欧元/21,900 英镑,按公式价格计算) 可能对 ER 不划算(占所有病例的 61%) 淋巴结阳性 HER2 早期乳腺癌患者,但对于 ER-/PR-亚型 (占所有病例的 37%) 至 69 岁的患者来说,成本效益高。曲妥珠单抗生物类似药的市场进入可能会将绝经前 ER/PR-癌症的 ICER 降低到这个阈值以下,但 ER/PR 癌症则不会。使用 ER 癌症最佳病例有效性测量的敏感性分析具有相同的结果。一个关键的限制是缺乏激素受体亚型的治疗效果数据。异质性仅限于年龄和激素受体状态; 肿瘤大小/等级异质性可在未来的工作中进行探索。这项研究强调了成本效益如何因年龄和激素受体亚型的异质性而有很大差异。资源分配和曲妥珠单抗等资助疗法的许可应考虑人口统计学和临床异质性; 目前在如何做出资金决策之间存在着深刻的脱节 (很大程度上与异质性无关) 以及个性化医学的原则。

adjuvant

免疫 佐剂 药物
概述  :  

佐剂(adjuvant)是一种非特异性免疫增强剂,预先或同抗原一起注射到机体,能增强机体对该抗原的免疫应答或改变免疫应答的类型。 免疫佐剂增强免疫应答的四种机制 1.改变抗原物理性状,延缓抗原降解和排除,延长在体内存留时间,延长抗原与免疫细胞作用时间,从而更有效的刺激免疫系统。 2.抗原在佐剂的辅佐作用下,更易被巨噬细胞吞噬和有效加工处理及呈递。 3.刺激单核/巨噬细胞活化,释放细胞因子调节和增强淋巴细胞免

adjuvant  英 /'ædʒʊv(ə)nt/ 美 /'ædʒəvənt/

释义    n.[医]佐剂,佐药

adj. 辅助的

短语    adjuvant therapy 辅助疗法

例句    To study the clinical effects of new adjuvant chemotherapy(NACT) on cervical carcinoma.探讨新辅助化疗(NACT)治疗宫颈癌的临床疗效。

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