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    Ivosidenib: an investigational drug for the treatment of biliary tract cancers

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    Authors
    Angelakas, Angelos
    Lamarca, Angela
    Hubner, Richard A
    McNamara, Mairead G
    Valle, Juan W
    Affiliation
    Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
    Issue Date
    2021
    
    Metadata
    Show full item record
    Abstract
    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 Drugs
    URI
    http://hdl.handle.net/10541/623856
    DOI
    10.1080/13543784.2021.1900115
    PubMed ID
    33683991
    Additional Links
    https://dx.doi.org/10.1080/13543784.2021.1900115
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1080/13543784.2021.1900115
    Scopus Count
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