New Treatment Option Emerges for Rare Form of Liver Bile Duct Cancer

Discovery published in the New England Journal of Medicine and includes University Hospitals Seidman Cancer Center researchers

Innovations in Cancer | Winter 2023

Patients who have a rare form of liver bile duct cancer caused by a specific genetic mutation may soon have a better treatment option that more successfully targets that mutation. That is the conclusion of a recent study in the New England Journal of Medicine, co-authored by University Hospitals Seidman Cancer Center’s Amit Mahipal, MD, Co-Lead, Gastrointestinal Disease Program, and colleagues across the country.

The research team tested the FGFR2 inhibitor futibatinib in 103 patients with unresectable or metastatic intrahepatic cholangiocarcinoma caused by specific FGFR2 gene alterations. These FGFR2 fusions or rearrangements occur in up to 14 percent of patients with this rare form of cancer. Patients in the study had previously received one or more types of systemic therapy. Results show that 42 percent of patients had a response to treatment with the new FGFR2 inhibitor, with the median duration of response of 9.7 months.

These results are especially important because of the limitations of other FGFR2 inhibitors in treating this poor-prognosis cancer, Dr. Mahipal says. Other FGFR2 inhibitors, pemigatinib and infigratinib, have received accelerated approval from the U.S. Food and Drug Administration for treating this form of cancer. But when they bind with receptors on the cancer cell, that binding process can sometimes be reversed and can result in new mutations in resistance to the therapy.

“The irreversible nature of binding and its distinct binding site make futibatinib less susceptible to on-target resistance mutations than pemigatinib and infigratinib,” Dr. Mahipal says. “In pre-clinical experiments, futibatinib showed stronger activity against a wider spectrum of FGFR2 mutations than other FGFR inhibitors. Furthermore, fewer drug-resistant clones emerged with futibatinib treatment. Data from this study establish futibatinib as having measurable clinical benefit in patients with this disease and show the value of molecular profiling in identifying tumors that are likely to respond to FGFR2 inhibition.”