An Overview of the Therapeutic Development of Cholangiocarcinoma with Special Emphasis on Targeted and Biologic Therapies

Purpose of Review Cholangiocarcinoma remains difficult to treat with a poor prognosis. Nevertheless, the treatment landscape is rapidly evolving to include chemotherapy, immunotherapy, and targeted therapies. This paper will summarize recent developments in targeted therapies. Recent Findings Gemcitabine/cisplatin plus durvalumab or pembrolizumab is the standard first-line treatment for patients with advanced cholangiocarcinoma. Multiple alterations have been identified with corresponding approved targeted agents, including fibroblast growth factor receptor inhibitors pemigatinib, infigratinib, and futibatinib; the isocitrate dehydrogenase 1 inhibitor ivosidenib; and the inhibitors of encoded kinases of NTRK1-3 entrectinib and larotrectinib. In tumors with microsatellite instability or deficient mismatch repair, pembrolizumab is approved. Dabrafenib and trametinib also received tumor agnostic approval for BRAF V600E mutations. Additional emerging targets include HER2 and DNA repair pathways. Summary Multiple targeted therapies are currently approved in the treatment of advanced cholangiocarcinoma, and many more molecular alterations or pathways have been identified as promising therapeutic targets.