{"title":"Ivosidenib:晚期胆管癌综述。","authors":"James E Frampton","doi":"10.1007/s11523-023-01002-3","DOIUrl":null,"url":null,"abstract":"<p><p>Ivosidenib (Tibsovo<sup>®</sup>), a first-in-class, oral small molecule, potent and selective inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), is approved in the EU and USA for the treatment of adults with pretreated, advanced, mIDH1 cholangiocarcinoma (CCA). It is presumed to exert its cytostatic effects in this setting by suppressing 2-hydroxyglutarate, an oncometabolite produced by mIDH1 that impairs cellular differentiation and promotes tumorigenesis. In the multinational phase 3 ClarIDHy study in patients with pretreated, advanced mIDH1 CCA, monotherapy with ivosidenib once daily significantly prolonged progression-free survival (PFS) and almost doubled the disease control rate compared with placebo. Moreover, it had a favourable effect on overall survival (OS), which was also significantly prolonged after correcting for a high rate of crossover from the placebo group (permitted by the trial protocol). Ivosidenib treatment preserved health-related quality of life (HRQOL) relating to physical function, pain and appetite loss/eating and was generally well tolerated, with the most common treatment-emergent adverse events being low-grade diarrhoea, nausea and fatigue. Thus, ivosidenib represents a novel and valuable targeted therapy for the subset of patients with pretreated, advanced CCA tumors harbouring mIDH1.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467016/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ivosidenib: A Review in Advanced Cholangiocarcinoma.\",\"authors\":\"James E Frampton\",\"doi\":\"10.1007/s11523-023-01002-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ivosidenib (Tibsovo<sup>®</sup>), a first-in-class, oral small molecule, potent and selective inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), is approved in the EU and USA for the treatment of adults with pretreated, advanced, mIDH1 cholangiocarcinoma (CCA). It is presumed to exert its cytostatic effects in this setting by suppressing 2-hydroxyglutarate, an oncometabolite produced by mIDH1 that impairs cellular differentiation and promotes tumorigenesis. In the multinational phase 3 ClarIDHy study in patients with pretreated, advanced mIDH1 CCA, monotherapy with ivosidenib once daily significantly prolonged progression-free survival (PFS) and almost doubled the disease control rate compared with placebo. Moreover, it had a favourable effect on overall survival (OS), which was also significantly prolonged after correcting for a high rate of crossover from the placebo group (permitted by the trial protocol). Ivosidenib treatment preserved health-related quality of life (HRQOL) relating to physical function, pain and appetite loss/eating and was generally well tolerated, with the most common treatment-emergent adverse events being low-grade diarrhoea, nausea and fatigue. Thus, ivosidenib represents a novel and valuable targeted therapy for the subset of patients with pretreated, advanced CCA tumors harbouring mIDH1.</p>\",\"PeriodicalId\":22195,\"journal\":{\"name\":\"Targeted Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467016/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Targeted Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11523-023-01002-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/10/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Targeted Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11523-023-01002-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Ivosidenib: A Review in Advanced Cholangiocarcinoma.
Ivosidenib (Tibsovo®), a first-in-class, oral small molecule, potent and selective inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), is approved in the EU and USA for the treatment of adults with pretreated, advanced, mIDH1 cholangiocarcinoma (CCA). It is presumed to exert its cytostatic effects in this setting by suppressing 2-hydroxyglutarate, an oncometabolite produced by mIDH1 that impairs cellular differentiation and promotes tumorigenesis. In the multinational phase 3 ClarIDHy study in patients with pretreated, advanced mIDH1 CCA, monotherapy with ivosidenib once daily significantly prolonged progression-free survival (PFS) and almost doubled the disease control rate compared with placebo. Moreover, it had a favourable effect on overall survival (OS), which was also significantly prolonged after correcting for a high rate of crossover from the placebo group (permitted by the trial protocol). Ivosidenib treatment preserved health-related quality of life (HRQOL) relating to physical function, pain and appetite loss/eating and was generally well tolerated, with the most common treatment-emergent adverse events being low-grade diarrhoea, nausea and fatigue. Thus, ivosidenib represents a novel and valuable targeted therapy for the subset of patients with pretreated, advanced CCA tumors harbouring mIDH1.
期刊介绍:
Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes:
Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches.
Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways.
Current Opinion articles that place interesting areas in perspective.
Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations.
Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement.
Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.