Precision approaches for cholangiocarcinoma: progress in clinical trials and beyond

Although a relatively uncommon tumor, the incidence of intrahepatic cholangiocarcinoma is rising globally. Unfortunately, most patients are diagnosed with locally advanced or metastatic disease with poor prognosis. Strategies targeting genomic alterations and incorporation of precision medicine will represent a new therapeutic avenue for these patients.

In this review article, we addressed clinical trials in cholangiocarcinoma with FGFR, IDH, BRAF, and ErbB2 targeted therapies. We also reviewed mechanisms of resistance to precision medicine and possible future strategies to overcome clonal evolution. Articles selected for this review were based on reported studies indexed in PubMed (2010-2021).

Pemigatinib, infigratinib and futibatinib could eventually be incorporated in the landscape of first-line systemic treatment for advanced cholangiocarcinoma with FGFR2 fusions or rearrangements after the ongoing phase III trials. Circulating tumor DNA could be used as a dynamic tool for evaluating mechanisms of resistance and prediction of response in patients treated with directed therapy.