Objective: Many patients with cholangiocarcinoma (CCA) are not surgical candidates, and the survival benefit of chemotherapy is less than 12 months. Several mutations and mutational clusters have recently been identified in CCA, some of which are pharmacologically targetable. The emergence of targeted therapies has significantly altered the treatment landscape of CCA and improved the prognosis for advanced or metastatic CCA. The purpose of this review is to describe past and current treatment strategies of CCA with a focus on FDA-approved targeted therapies.
Data sources: A systematic evaluation of all FDA-approved targeted treatments for CCA through October 2022 was conducted. Information related to pharmacology, clinical efficacy, and safety was gathered from the package insert, and clinical trial data.
Data summary: As of the writing of this review, four targeted agents are FDA approved for the treatment of locally advanced or metastatic CCA. These agents include the IDH1 inhibitor ivosidenib and the FGFR2 inhibitors pemigatinib, infigratinib, and futibatinib. Collectively, these agents have provided additional treatment options for select patients with previously treated locally advanced or unresectable CCA. These agents have also contributed to the development of other targeted therapies for the treatment of CCA and have opened the door for the exploration of novel treatment combinations such as chemotherapy and immunotherapy, which have recently become a front-line treatment option.
Conclusions: Four targeted small molecule agents have emerged as effective therapies in the second-line setting for CCA, which has immensely changed the treatment landscape and directly led to further investigation of targeted agents and immunotherapy as treatment for CCA.
Keywords: Cholangiocarcinoma; biliary tract cancer; molecular targeted therapies; pharmacotherapy.