ABSTRACT
BACKGROUND: Precision medicine with genomic analyses of tumour tissue has introduced tumour-agnostic therapies in oncology. CASE PRESENTATION: A previously healthy woman in her thirties was diagnosed with advanced cholangiocarcinoma. She received four courses of cisplatin and gemcitabine, but her disease progressed. RNA-based next-generation sequencing revealed a fusion transcript involving RBPMS-NTRK3. She commenced entrectinib 600 mg OD and after five days reported clinical improvement. CT scans after five weeks of treatment confirmed response. She experienced some toxicities, such as mild chest pain with slight increase in troponin, urinary retention (successfully treated with mirabegron 50 mg daily), dysaesthesia, constipation and dysgeusia. Echocardiography and coronary angiography were performed without pathology. Dosing was reduced to 400 mg daily after six weeks, and she has received treatment without significant side effects and with normal troponin for five months. INTERPRETATION: This example shows the importance of implementing next-generation sequencing of tumours and access to tumour-agnostic cancer treatment.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Pharmaceutical Preparations , Adult , Bile Ducts, Intrahepatic , Female , Humans , Receptor Protein-Tyrosine KinasesABSTRACT
The use of immune checkpoint inhibitors has dramatically improved the chance of surviving malignant melanomas; however, the effect comes at the cost of toxicities that are difficult to predict. Immune-mediated hepatitis is the most common form of liver toxicity, but fatal outcome is uncommon. We report the case of a 70-year-old female with metastatic malignant melanoma who developed severe liver toxicity characterized by bile duct injury and cholestasis. The condition progressed despite potent immunosuppressive treatment, plasmapheresis, and intensive supportive care; and the patient died while still having tumor response.
