Ivosidenib: an investigational drug for the treatment of biliary tract cancers
Affiliation
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UKIssue Date
2021
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Introduction: Biliary tract cancers (BTCs) [including cholangiocarcinoma and gallbladder cancer] are rare cancers associated with poor survival; most patients have advanced disease at diagnosis. Current chemotherapy reference regimens include cisplatin and gemcitabine as first-line and oxaliplatin and 5-fluorouracil (FOLFOX) in second-line. Molecular profiling has identified several actionable therapeutic targets including isocitrate dehydrogenase (IDH)1 mutations. Ivosidenib is a reversible inhibitor of mutant IDH1; it is currently approved for the treatment of acute myeloid leukaemia and has been studied in patients with advanced cholangiocarcinoma. Areas covered: This article introduces current treatments for BTC and sheds light on the mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy and safety of ivosidenib in advanced cholangiocarcinoma. The authors conclude with insights on the changing treatment paradigm created by emerging drugs and precision approaches. Expert opinion: Ivosidenib is well-tolerated, with good oral exposure and long half-life as shown by phase I data. In a phase III study, ivosidenib has demonstrated improved progression-free survival compared to placebo (median 2.7 vs 1.4 months; hazard ratio 0.37; 95% confidence interval 0.25-0.54; one-sided p<0.0001); it has also demonstrated a trend towards increased overall survival in patients with cholangiocarcinoma and disease progression on prior chemotherapy. Final survival data from this study are pending presentation. Increased use of molecular profiling will continue to identify potential therapeutic targets and improve the prognosis of patients with these cancers.Citation
Angelakas A, Lamarca A, Hubner RA, McNamara MG, Valle JW. Ivosidenib: an investigational drug for the treatment of biliary tract cancers. Expert Opin Investig Drugs. 2021.Journal
Expert Opinion in Investigational DrugsDOI
10.1080/13543784.2021.1900115PubMed ID
33683991Additional Links
https://dx.doi.org/10.1080/13543784.2021.1900115Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1080/13543784.2021.1900115
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