FGFR2 might be a promising therapeutic target for some types of carcinomas: Analysis of 1312 tumors with FGFR2 abnormalities

Background: Genetic abnormalities of the fibroblast growth factor receptor 2 ( FGFR2 ) gene, including amplification, fusions, and mutations, have been reported in various solid tumors. While molecular targeted therapies against FGFR2 fusion have been proved to be useful in cholangiocarcinoma, the therapeutic significance of FGFR2 inhibitors remains unclear in other various solid cancers. Genomic and clinical information from solid tumor cancer gene panel testing cases is consolidated in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. This study aimed to utilize the C-CAT database to clarify the clinical-pathological significance of FGFR2 abnormalities. Materials & Methods: A total of 101,231 patients with solid cancer have been registered in the C-CAT database between June 2019 and June 2025. Of the 101,231 cases, 1312 cases with FGFR2 gene abnormalities were analyzed. Tumor type distribution, co-mutations, and responses to FGFR inhibitors were evaluated. Disease control rate (DCR) was assessed in patients who received FGFR-targeted therapy. Result: FGFR2 alterations included amplification in 515 cases, fusion in 280 cases, and mutations in 568 cases. Their abnormalities were detected most frequently in the biliary tract (271 cases), esophagus/stomach (231 cases), and breast (211 cases). Amplification was frequent in the esophagus/stomach (205 cases) and breast (105 cases). FGFR2 fusions are frequently detected in the biliary tract (163 cases), followed by breast (21 cases), pancreas (13 cases). Mutations were frequent in the uterus (111 cases), breast (89 cases), and biliary tract (86 cases). Among 1312 FGFR2 alteration cases, FGFR2 inhibitors were administered in 85 cases. Of the 85 cases, DCR was achieved in 49 cases, 44 cases of which were biliary tract cancer. Conclusions: FGFR2 might be a promising therapeutic target not only for cholangiocarcinoma with fusion but also for esophagus/stomach cancer and breast cancer with FGFR2 alterations.