Precision Medicine: an Intrahepatic Cholangiocarcinoma with a Novel RBPMS-MET Fusion Sensitive to Crizotinib

Background: Intrahepatic cholangiocarcinoma is a malignant tumor that starts from the epithelium of the bile duct and has a poor prognosis. They are characterized by poor response to chemotherapy and lack of effective targeted therapies; thus, therapeutic options are limited.

Case Presentation: A 59-year-old man was admitted to the hospital for a workup of abnormal CA19-9 levels. He was diagnosed with ICC, underwent surgery and was found to have pT1bNx disease. He developed rapid disease recurrence on adjuvant gemcitabine + capecitabine. Following recurrence, he received first-line systemic pembrolizumab + lenvatinib and second-line pembrolizumab + lenvatinib + chemotherapy and had mild tumor regression followed by progression. Next-generation sequencing was performed on the baseline surgical sample. This revealed a novel RBPMS-MET fusion, and based on the literature, crizotinib 250 mg twice a day was administered. After 3 months of crizotinib treatment, magnetic resonance imaging revealed a significant reduction in liver lesions, and 4 months after initiating treatment, scans demonstrated a partial response.

Conclusion: Our case report strengthens the evidence that crizotinib may be a viable treatment option for patients with ICC with a c-MET tyrosine kinase fusion, necessitating additional clinical investigation.