| Abstract: |
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). © 2025 The Author(s) |
