Abstract
Introduction: Biliary tract cancer (including cholangiocarcinoma and gallbladder cancer) is rare and 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 targets and in this review we focus on isocitrate dehydrogenase (IDH)1 mutations. Ivosidenib is a reversible inhibitor of mutant IDH1; currently approved for the treatment of acute myeloid leukaemia, it has also been studied in patients with advanced cholangiocarcinoma.
Areas covered: The mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy and safety of ivosidenib in advanced cholangiocarcinoma are discussed.
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) as well as 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 potentially-therapeutic targets and thereby improve the prognosis of patients with these cancers.
| Original language | English |
|---|---|
| Journal | Expert Opinion on Investigational Drugs |
| Publication status | Accepted/In press - 3 Mar 2021 |
