Lirafugratinib Approval Adds a Third FGFR2 Inhibitor in Cholangiocarcinoma

The FDA approval of lirafugratinib (Lyrfigtu) for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma gives clinicians a third FGFR2 inhibitor for patients with FGFR2 fusion–positive disease. Since the first agents in this class reached the market, the field has also developed a clearer picture of how tumors escape them.

In an interview with CancerNetwork® following the 2026 Chicago Cholangiocarcinoma Symposium, Chih-Yi “Andy” Liao, MD, shared his thoughts on the approval, noting that his institution participated in the clinical trial that supported it. Liao explained that the 3 approved FGFR inhibitors cannot be compared head-to-head because they were studied in different patient populations and differ from one another, but that all demonstrate efficacy in FGFR2 fusion–positive cholangiocarcinoma and have a place in practice and research. He also described what has been learned about resistance, including the acquisition of gatekeeper mutations in the FGFR2 molecule, and noted that next-generation agents such as lirafugratinib were designed with those mutations in mind.

Liao is an associate professor of Medicine, associate director of Gastrointestinal Oncology, and co-director of the Neuroendocrine Tumor program at University of Chicago School of Medicine.

Transcript:

CancerNetwork: The FDA recently approved lirafugratinib, the third FGFR2 inhibitor in cholangiocarcinoma. What are your thoughts on the agent?

Liao: We were part of the clinical trial that led to the approval... so we’re super excited to have yet another FDA approval for cholangiocarcinoma. That’s always a win for our patients, and now we have 3 FDA-approved FGFR inhibitors on the market. We can look at each of the individual trials and the data separately. We can’t compare them head-to-head because they’re different patient populations, and these drugs are all slightly different. But all of them show efficacy for [FGFR2 fusion–positive] cholangiocarcinoma, so I think they all have a place in our clinical practice and in our research. We’ve learned a lot more since the first FGFR inhibitors came out about how tumors become resistant to FGFR inhibitors. One of the mechanisms is that they can acquire additional mutations called gatekeeper mutations in the FGFR2 molecule, and so some of these next-generation drugs, like lirafugratinib, were designed with this in mind to overcome some of these resistance mutations.

Reference

1. FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. News release. FDA. September 23, 2026. Accessed September 28, 2026. https://tinyurl.com/mst6kcav