Resistance Patterns Shape FGFR Inhibitor Sequencing in Cholangiocarcinoma

In this episode, we spoke with Arndt Vogel, MD, a faculty member at the University of Toronto Institute of Medical Science, a scientist at the Toronto General Hospital Research Institute, and a medical oncologist at the UHN–Princess Margaret Cancer Centre in Canada.

In our exclusive interview, Dr Vogel highlighted the rationale and growing evidence for sequential FGFR inhibition in FGFR2 fusion–positive cholangiocarcinoma, explaining that on-target resistance mutations and the differing binding properties of agents like pemigatinib (Pemazyre), futibatinib (Lytgobi), and the more selective tinengotinib (TT-00420) support using these drugs in sequence, although he emphasized that treatment decisions remain biomarker-informed rather than biomarker-guided. He also stressed the importance of early, RNA-based next-generation sequencing, the emerging role of circulating tumor DNA in capturing polyclonal resistance, and his anticipation of forthcoming phase 3 tinengotinib data.