Dr Baretti on the Utility of FGFR Inhibitors in FGFR2+ Intrahepatic Cholangiocarcinoma

Marina Baretti, MD, assistant professor, oncology, Johns Hopkins University, Johns Hopkins Hospital, discusses the evolving utility of FGFR inhibitors in the treatment of patients with unresectable, advanced, or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other rearrangements.

The oncology field has made notable progress in transitioning molecularly targeted therapies from experimental stages to clinical application, Baretti begins. Infigratinib (Truseltiq) was among the initial medications to receive an FDA approval for patients with FGFR2+ cholangiocarcinoma in 2021 based on findings from a phase 2 study (NCT02150967). However, the commercialization of infigratinib was discontinued by the manufacturing company in 2022,rendering the agent currently unavailable, Baretti emphasizes. However, 2 other agents are available for patients with cholangiocarcinoma: pemigatinib (Pemazyre) and futibatinib (Lytgobi).

Pemigatinib became the first FDA-approved FGFR2 inhibitor for patients with advanced, metastatic, or surgically unresectable cholangiocarcinomas carrying FGFR2 fusions based on findings from the phase 2 FIGHT-202 study (NCT02924376), she expands. The study enrolled pretreated patients whose disease had progressed following 1 or more prior lines of therapy and produced highly encouraging results with pemigatinib. These positive outcomes includedimproved median progression-free survival (PFS) and overall survival (OS) with pemigatinib compared with historical data from chemotherapy-based therapies in the second-line setting and beyond, Baretti explains.

Furthermore, in 2022, futibatinib received FDA approval for patients with FGFR2+ cholangiocarcinoma. Futibatinib acts as an irreversible inhibitor by binding to the FGFR ATP binding pocket, Baretti states. Notably, futibatinib was evaluated in a phase 1/2 study (NCT02052778) in a global population of patients with advanced solid tumors harboring FGFR2fusions or rearrangements. This trial exhibited positive results in the cholangiocarcinoma cohort, and the PFS and OS data with futibatinib in this cohort outperformed historical data with chemotherapy in patients with cholangiocarcinoma, she adds.

The spectrum of FGFR-targeted therapies continues to expand rapidly, with some novel agents under current investigation, Baretti continues. Yet, questions remain about the optimal sequential use of these targeted agents in clinical practice, she concludes.