Abstract B048: Fibroblast Growth Factor Receptor 2 Alterations in non-Cholangiocarcinoma Gastrointestinal Tumors

Abstract Introduction: Fibroblast growth factor receptor 2 (FGFR2) fusions (f) or rearrangements (r), are main oncogenic drivers in cholangiocarcinoma. These alterations can be found in other gastrointestinal (GI) tumors but are not well described, with some data showing the efficacy of anti-FGFR especially in gastric cancer. Methods: This is a retrospective study including patients (pts) with GI tumors harboring FGFR2 aberrations treated at Gustave Roussy cancer center from 2011. Patient’s and tumors characteristics as well as the different types of FGFR2 alterations, were described. Overall survival (OS) using Kaplan Meier were calculated .The impact of anti-FGFR treatment was evaluated also of pts treated with anti-FGFR therapies. Results: A total number of 21 pts were included. Most pts were males and the median age at diagnosis was 59 years [37-76 years]. 11 pts had gastric adenocarcinoma (ADK), 5 pts with pancreatic ADK, 2 colon ADK, 2 duodenal ADK and 1 squamous cell anal carcinoma. All gastric ADK showed poorly differentiated histology, including 7 cases with a signet ring cell component. 15 pts were metastatic at initial diagnosis and the rest developed metastases during disease evolution. The most common metastatic sites were: lymph nodes (57%), lung (38%), peritoneal (33%) and liver (29%). All pts had a liquid biopsy and 3 pts had both liquid biopsy and tissue molecular profile. FGFR2 aberrations were amplifications (a) (N=8), f (N=11), other r (N=7) and mutations (m) (N=4). 1 pt had both FGFR2a and r, and 4 pts had FGFR2a,f,r. The FGFR2 fusion partners were: INA, TACC2, CTNNB1, CTNNA3, IGHMBP2, PPAPDC1A, NEK1, CCSER2, CGNL1 and KCTD1. 12 pts received anti-FGFR therapy, including 4 who underwent 2 different anti-FGFR regimens and 2 who received 3 successive anti-FGFR treatments. 4 pts received anti-FGFR therapy in 2nd line, and the others received it in the third line or later. Median OS of the overall population was 27.36 months [11.63-48.10 months]. Despite numerical advantage in median OS (34.8 months [22.5-50.7 months), there was no statistically significant difference between patients treated or not with anti-FGFR therapies (p=0.37). Pts with FGFR2a had a median OS of 26.7 months [8.7-49.0 months] whereas pts with FGFR2a,f/r had a median OS of 49 months [27.6-62.9 months]. Conclusion: Our results demonstrated an association between FGFR2 alterations and poorly differentiated histology in gastric ADK, as well as a high prevalence of lymph node metastases across different GI cancers. The FGFR2 fusion partners identified were distinct from those typically seen in cholangiocarcinomas. Despite the limited number of pts, our study highlights the need to further investigate FGFR2 alterations as potential oncogenic drivers in GI malignancies and as actionable therapeutic targets. Citation Format: Charbel Soueidy, Damien Vasseur, Christophe Massard, Antoine Hollebecque, Cristina Smolenschi. Fibroblast Growth Factor Receptor 2 Alterations in non-Cholangiocarcinoma Gastrointestinal Tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B048.