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...
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Elsevier
2025-06-01
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| Series: | ESMO Gastrointestinal Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949819825000287 |
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| author | 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 |
| author_facet | 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 |
| author_sort | J.W. Valle |
| collection | DOAJ |
| description | 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). |
| format | Article |
| id | doaj-art-2ca207c8635a4451ae0fd019a8dcda12 |
| institution | OA Journals |
| issn | 2949-8198 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | ESMO Gastrointestinal Oncology |
| spelling | doaj-art-2ca207c8635a4451ae0fd019a8dcda122025-08-20T02:07:23ZengElsevierESMO Gastrointestinal Oncology2949-81982025-06-01810015910.1016/j.esmogo.2025.100159Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinomaJ.W. Valle0G.K. Abou-Alfa1R.K. Kelley2M.A. Lowery3R.T. Shroff4Y. Bian5G. Saint-Hilary6H. Liu7Z. Teng8Z. Hua9C. Gliser10A. Vogel11M.M. Javle12Cholangiocarcinoma Foundation, Salt Lake City, USA; Division of Cancer Sciences, University of Manchester, Manchester, UK; Correspondence to: Prof. Juan W. Valle, Cholangiocarcinoma Foundation, 5526 West 13400 South, #510 Herriman, Salt Lake City, UT 84096, USA. Tel: +1-385-218-3013Memorial Sloan Kettering Cancer Center, New York; Weill Medical College at Cornell University, New York, USA; Trinity College Dublin, Dublin, IrelandDivision of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San FranciscoTrinity College Dublin, Dublin, IrelandUniversity of Arizona Cancer Center, TucsonServier Pharmaceuticals, Boston, USASaryga, Tournus, FranceServier Pharmaceuticals, Boston, USAServier Pharmaceuticals, Boston, USAServier Pharmaceuticals, Boston, USAServier Pharmaceuticals, Boston, USAHannover Medical School, Hannover, Germany; Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto; Medical Oncology, Princess Margaret Cancer Centre, Toronto, CanadaMD Anderson Cancer Center, Houston, USABackground: 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).http://www.sciencedirect.com/science/article/pii/S2949819825000287quantitative drug benefit–risk assessmentcholangiocarcinomamutant isocitrate dehydrogenase-1ivosidenib |
| spellingShingle | 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 Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma ESMO Gastrointestinal Oncology quantitative drug benefit–risk assessment cholangiocarcinoma mutant isocitrate dehydrogenase-1 ivosidenib |
| title | Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma |
| title_full | Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma |
| title_fullStr | Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma |
| title_full_unstemmed | Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma |
| title_short | Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma |
| title_sort | quantitative benefit risk assessment of data from the phase iii claridhy study of ivosidenib versus placebo in patients with midh1 cholangiocarcinoma |
| topic | quantitative drug benefit–risk assessment cholangiocarcinoma mutant isocitrate dehydrogenase-1 ivosidenib |
| url | http://www.sciencedirect.com/science/article/pii/S2949819825000287 |
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