Patients with cholangiocarcinoma who have alterations in the fibroblast growth factor receptor (FGFR) gene tolerate ponatinib treatment well, a new study published in the journal Investigational New Drugs found.

The authors stated that this is the first report of prospective assessment of FGFR inhibition in cholangiocarcinoma using ponatinib, and the first study to report the effect of the treatment on patients’ health-related quality of life.

FGFR alterations occur in about 15% of intrahepatic cholangiocarcinoma cases. Preclinical and early clinical studies have shown that inhibiting the FGFR pathway leads to antitumor activity and may be a promising therapeutic strategy in patients with cholangiocarcinoma with altered FGFR. Ponatinib is a multitargeted tyrosine kinase inhibitor with activity against FGFR

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To test whether ponatinib would be active in cases of cholangiocarcinoma with FGFR alterations, a group of researchers led by Mitesh J. Borad, MD, of the Mayo Clinic in Rochester conducted a multicenter pilot study in 12 patients. During the study, 1 of the 12 patients demonstrated partial responses to ponatinib treatment. The median progression-free survival for all patients was 2.4 months. The median overall survival was 15.7 months. 

All of the toxicities that the researchers observed were mild, manageable, and reversible. The most common toxicity was lymphopenia affecting 75% of patients, followed by rash affecting 63%, and fatigue affecting 50% of the patients. There was no significant detriment in global quality of life.

The researchers concluded that ponatinib as a single agent is tolerable with no significant detriment on quality of life. However, they said it only has modest clinical activity compared to small molecule inhibitors specific to FGFR, and the clinical activity of the treatment is limited. “The limited anti-tumor activity from ponatinib may in part be from its multitargeted activity compared to other agents with more FGFR selectivity,” they wrote.


Ahn DH, Uson Junior PLS, Masci P, et al. A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma. Invest New Drugs. Published online August 31, 2021. doi:10.1007/s10637-021-01170-x