Advanced Cholangiocarcinoma: FGFR2 Inhibitors vs Chemo

Saeed Sadeghi, MD: The majority of the FGFR2 inhibitors, including pemigatinib and infigratinib, are highly selective for the FGFR1, FGFR2, and FGFR3 receptors. There is some variability in terms of their off-target activity against the VEGF receptor as well as FGFR4 receptor. FGFR4 seems to be mitigating the diarrhea that is associated with these compounds and also may be mitigating, for example, the dry eyes that are seen. As a result, a drug that has less selectivity for FGFR4 can potentially have fewer instances of diarrhea and dry eyes.

If you look at the data that are available for second-line chemotherapy, the results are quite dismal. The progression-free survival [PFS] ranges from about 2 to maybe 4 months. Overall survival ranges from 6 to 8 months. The response rate is in the single digits—6%. When you compare that with pemigatinib data and infigratinib data, we see a stark difference. Both of these agents have response rates in the 30% range, and they certainly have a PFS that is longer than what we see with second-line chemotherapy—around 6.8 months.

Transcript edited for clarity.