ididhy III期研究数据的定量获益-风险评估ivosidenib与安慰剂在mIDH1胆管癌患者中的应用

J.W. Valle , G.K. Abou-Alfa , R.K. Kelley , M.A. Lowery , R.T. Shroff , Y. Bian , G. Saint-Hilary , H. Liu , Z. Teng , Z. Hua , C. Gliser , A. Vogel , M.M. Javle
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引用次数: 0

摘要

定量药物获益-风险评估(BRA)有助于评估新癌症疗法的获益和风险程度。本BRA旨在利用关键III期ClarIDHy研究的数据,总结ivosidenib与安慰剂治疗既往治疗、局部晚期或转移性突变异柠檬酸脱氢酶-1胆管癌的获益和风险证据。材料和方法血管癌专家确定了伊沃sidenib和安慰剂的相关关键获益和风险标准,以创建价值树并确定了尺度和权重。然后将多标准决策分析建模方法应用于ClarIDHy数据,以估计ivosidenib的获益-风险概况优于安慰剂的概率。结果187例患者随机分为伊沃西替尼500 mg组(n = 126)和安慰剂组(n = 61)。初步分析[量表损失评分(SLoS)模型]显示,伊沃西迪尼与安慰剂相比,获益-风险谱的概率为95.24%。将sls模型应用于备选集,将线性模型和产品模型应用于价值树中获益和风险标准的主集和备选集的敏感性分析也显示,在所有评估的终点上,伊沃sidenib优于安慰剂的获益-风险概况的概率一致较高(sls模型:95%;线性模型:>;99%;产品型号:>;94%)。同样,随机权重分析也倾向于ivosidenib,所有评估的权重和结果都很快向主要分析结果收敛。这些结果提供了全面的证据,表明ivosidenib是一种有效的治疗方法,具有可耐受的安全性,支持先前的数据(ClinicalTrials.gov NCT02989857)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma

Background

Quantitative drug benefit–risk assessment (BRA) helps assess the magnitude of benefit and risk of new cancer therapies. This BRA aimed to summarize the evidence for the benefits and risks of ivosidenib versus placebo for the treatment of previously treated, locally advanced or metastatic mutant isocitrate dehydrogenase-1 cholangiocarcinoma using data from the pivotal phase III ClarIDHy study.

Materials and methods

Cholangiocarcinoma experts determined relevant key benefit and risk criteria for ivosidenib and placebo to create a value tree and determined scales and weights. Multi-Criteria Decision Analysis modelling approaches were then applied to the ClarIDHy data to estimate the probability that the benefit–risk profile of ivosidenib was better than that of placebo.

Results

A total of 187 patients were randomly assigned to ivosidenib 500 mg (n = 126) or placebo (n = 61). The primary analysis [Scale Loss Score (SLoS) model] showed a 95.24% probability for the benefit–risk profile favoring ivosidenib versus placebo. Sensitivity analyses applying the SLoS model to alternative sets, and the linear and product models to the main and alternative sets, of benefit and risk criteria in the value tree also showed consistently high probability for the benefit–risk profile favoring ivosidenib versus placebo for all endpoints evaluated (SLoS model: >95%; linear model: >99%; product model: >94%). Similarly, the random weights analysis favored ivosidenib with all evaluated weights and results converging quickly towards the main analysis results.

Conclusions

These results provide comprehensive evidence that ivosidenib is an effective treatment with a tolerable safety profile for this aggressive disease, supporting previous data (ClinicalTrials.gov NCT02989857).
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