Case Report: Response to ivosidenib in patients with cholangiocarcinoma: a clinical perspective with illustrative cases

Cholangiocarcinoma (CCA) is a rare cancer, rich in molecular targets. Molecular targeted therapy is the recommended second-line approach for patients with advanced or metastatic CCA, including ivosidenib for patients with mutations in the gene for isocitrate dehydrogenase 1 ( IDH1). Herein, three case studies of patients with CCA who received ivosidenib are presented, to illustrate key issues relevant to the use of this treatment in clinical practice. The first case demonstrates a durable response to ivosidenib treatment lasting 1 year, as seen in the phase 3 ClarIDHy study, where most responders had stable disease and the presence of a response significantly prolonged survival, particularly in those with a response lasting 1 year (2-year survival rate of 92%). The second case illustrates tumor shrinkage with ivosidenib, which was seen in only 2% of patients in the ClarIDHy study. This patient had both IDH1 and human epidermal growth factor receptor 2 ( HER2 ) mutations, providing more than one targeted treatment option, but chose oral therapy with ivosidenib. The third case describes some of the challenges when managing CCA in older patients, particularly if performance status (PS) is impaired. Because of the patient’s advanced age and frailty, she began first-line ivosidenib as off-label treatment. Although she experienced significant improvement in PS, she developed malignant hypercalcemia. The risk of hypercalcemia may be higher in older patients and those with IDH1 mutations. These cases illustrate the potential benefits of ivosidenib, in terms of clinical response, quality of life, and tolerability. They also highlight the importance of obtaining adequate biopsy samples for molecular testing at diagnosis to identify potential targetable mutations. Performing molecular testing (in the absence of adequate tumor tissue with liquid biopsy) as early as possible is already an integral part of the treatment pathway planning for CCA patients. Early molecular testing may therefore lead to the possibility of administering targeted therapy in the first-line setting within this patient group, pending the outcomes of clinical trials.