Learnings from trials like FIGHT-302 reveal that resistance to targeted therapy occurs both on-target (kinase domain) and off-target (e.g., MAP kinase pathway). The next research frontier is likely not just developing better inhibitors, but combining them with chemotherapy to potentially block multiple resistance pathways simultaneously from the outset.
The FIGHT-302 trial for FGFR2-rearranged cholangiocarcinoma closed early, like similar trials, because the standard of care evolved faster than patients could be recruited. This highlights a fundamental challenge in studying rare molecular subtypes, requiring alternative trial designs where thousands of patients must be screened to find a few eligible participants.
Despite showing superior progression-free survival over chemotherapy, the FIGHT-302 trial doesn't establish pemigatinib as an automatic first choice or a "slam dunk." It solidifies its role as a strong option, with the final decision depending on patient preferences, tumor characteristics, and a detailed discussion of pros and cons versus chemo-immunotherapy.