A Next-Generation FGR2 Inhibitor for Intrahepatic Cholangiocarcinoma

In biliary cancers that harbor fibroblast growth factor receptor 2 (FGFR2) gene fusions or rearrangements, inhibitors of FGFR2 have significant and often durable activity. Investigators now report the results of an international, industry-sponsored, open-label, phase 2 trial of futibatinib — an oral irreversible inhibitor of FGFR2 — in patients with previously treated advanced biliary cancer with FGFR2 alterations.

Of 798 patients with intrahepatic cholangiocarcinoma undergoing tissue-based screening, 103 with FGFR2 alterations were enrolled and treated with futibatinib (20 mg daily). The median age was 58, most patients (56%) were female, most (78%) had FGFR2 gene fusions as opposed to rearrangements (22%), and most (51%) had received 2 or more prior chemotherapy regimens.

Objective response — the primary outcome — occurred in 42% of patients, and 83% achieved disease control. At a median follow-up of 17.1 months, median duration of response was 9.7 months, and median progression-free survival was 9.0 months. Median overall survival was 21.7 months. In analysis of patients' molecular profiling data, no concurrent gene alterations had an impact on efficacy of therapy. Blood-based circulating tumor DNA testing prior to therapy identified FGFR2 gene fusions and rearrangements in 87% of patients evaluated.

The most common grade 3 or higher treatment-related adverse events included hyperphosphatemia in 30% (with no patients discontinued for this toxicity) and stomatitis, fatigue, and increase in aspartate aminotransferase in 6% to 7% of patients.