How would you approach the treatment of metastatic cholangiocarcinoma after progression on gemcitabine/cisplatin, FOLFOX, and pemigatinib?

This is a tough situation. Depending on the patient's performance status and organ function, a clinical trial is strongly recommended. If the patient has FGFR2 fusion or chromosome rearrangement with prior exposure to pemigatinib, resistance mutation (gatekeeper mutation) is likely present and may be overcome with more potent and selective FGFR inhibitors. NCT04526106 is an example. This trial is testing RLY-4008, a potent and highly selective FGFR2 inhibitor. It is recruiting patients with adva...

In reference to the question about switching from one FGFR inhibitor to another, that is a great thought that we have been navigating for a while, with the presumption of potential resistance to one of the anti-FGFR2 and alternating to another (see Goyal et al., PMID 28034880 for a model of varying sensitivities to different FGFR agents). The question is would we need to know what genetic alteration the tumor may acquire and would we know which of the antiFGFR2 would be best to address it? This ...

Agree with the excellent comments above. If no access for a trial of a more potent FGFRi and preserved PS, would also consider FOLFIRI/ NALIRI chemotherapy based on NIFTY trial in addition to the options mentioned above, especially if neuropathies are an issue.