Are FGFR and IDH1-2 alterations a positive prognostic factor in intrahepatic cholangiocarcinoma? An unresolved issue

Abstract

Despite representing some of the most common and investigated molecular changes in intrahepatic cholangiocarcinoma (iCCA), the prognostic role of FGFR and IDH1/2 alterations still remains an open question. In this review we provide a critical analysis of available literature data regarding this topic, underlining the strengths and pitfalls of each study reported. Despite the overall poor quality of current available studies, a general trend toward a better overall survival for FGFR2 rearrangements and, possibly, for FGFR2-3 alterations can be inferred. On the other hand, the positive prognostic role of IDH1/2 mutation seems much more uncertain. In this scenario, better designed clinical trials in these subsets of iCCA patients are needed in order to get definitive conclusions on this issue.

What Role Does Radiotherapy Play in the Molecular Era for Intrahepatic Cholangiocarcinoma?

“…In retrospective studies, patients with FGFR GAs may have better prognosis than those without FGFR GAs, 31 but these studies had notable biases and require further prospective validation. 32 With the recognition that multiple solid cancers including iCCA have FGFR GAs, a series of clinical trials have shown promising response rates and durable control of oral medications that target various FGFR GAs. A selective pan-FGFR kinase inhibitor infigratinib had an overall response rate of 14.8%, disease control rate of 75.4%, and median PFS of 5.8 months, leading to FDA approval of the drug for patients with FGFR2 fusions or other alterations.…”

Clinical experience with pemigatinib for previously treated metastatic cholangiocarcinoma: practical considerations from clinical cases

“…19 The current evidence suggests a prognostic role of FGFR2 rearrangements and, possibly, for FGFR2 or FGFR3 alterations in patients with iCCA. 20 Early clinical trials showed limited antitumour activity of nonselective FGFR tyrosine kinase inhibitors in CCA. [21][22][23] However, the introduction of selective FGFR inhibitors has significantly improved the response and survival of patients with advanced CCA with FGFR2 fusion or rearrangement.…”