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Author: Admin | 2025-04-28
Ivosidenib. No new safety signals were observed during long-term treatment with ivosidenib. Introduction Cholangiocarcinoma (CCA) is the second most common primary liver tumor after hepatocellular carcinoma. CCA includes malignancies of the intrahepatic cholangiocarcinoma (iCCA) and extrahepatic bile ducts and the gallbladder [1]. CCA has been steadily increasing worldwide over the past few decades, with a current incidence of 6 per 100,000 [2]. Only 30% of patients are eligible for resection at the time of diagnosis [3], and the risk of recurrence is up to 40% [4]. Chemotherapy with gemcitabine and cisplatin has been the standard of care for patients with unresectable or metastatic disease for more than a decade. At this stage, median overall survival (mOS) is less than 12 months and the 5-year survival rate is less than 20% [5]. Recently, the phase 3 TOPAZ-1 and KEYNOTE-966 trials both showed a small but significant additional improvement in mOS with the addition of the checkpoint inhibitors durvalumab or pembrolizumab to gemcitabine and cisplatin [6, 7]. The mOS of patients with CCA after progression on first-line therapy is less than 3 months [8, 9]. For eligible patients, second-line chemotherapy provides a small survival benefit, with the best therapeutic regimen selected based on its specific side effects [1]. CCA, especially iCCA with small duct histology, is enriched by genomic alterations which can be exploited as actionable therapeutic targets. Therefore, molecular profiling of the tumor is strongly recommended for these patients. The most common targetable alteration found in iCCA is a heterozygous point mutation in codon 132 of the isocitrate dehydrogenase 1 (IDH1) gene encoding arginine (R132), which occurs in approximately 14% of cases [10]. IDH1 normally functions to catalyze the oxidative carboxylation of isocitrate to α-ketoglutarate. Instead, mutated IDH1 has neomorphic activity that converts α-ketoglutarate to the oncometabolite 2-hydroxyglutarate, resulting in intracellular
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