FGFR-targeted therapies in advanced esophagogastric cancer: A systematic review and meta-analysis.

Abstract

e16053 Background: Esophagogastric cancer carries high mortality, with most patients diagnosed at advanced stages. In HER2-negative disease, chemotherapy ± nivolumab is standard, but yields limited survival. Alterations in the fibroblast growth factor receptor (FGFR) pathway are present in 5-10% of gastric and gastroesophageal junction cancer and confer aggressive biology. The objective of this systematic review and meta-analysis is to assess the efficacy and safety of FGFR inhibitors as second line agents in adults with advanced or metastatic esophagogastric adenocarcinoma. Methods: A systematic review following PRISMA guidelines was conducted using PubMed, Embase, Cochrane, and ClinicalTrials.gov through December 2025. Studies evaluating FGFR inhibitors in adults with advanced or metastatic esophagogastric adenocarcinoma were included. Efficacy and safety outcomes were extracted. We pooled the outcomes using a random-effects inverse-variance meta-analysis of proportions, with heterogeneity quantified by I². Analyses were conducted in R. Results: Our study comprised three articles with a total of 195 patients, including 145 (74.4%) males and 50 (25.6%) females, with a median age of 61.3 (59–65) years. Patients had advanced, metastatic, or unresectable esophagogastric or gastroesophageal junction adenocarcinoma and were treated with FGFR-targeted agents as a second line therapy: pemigatinib in 8 patients (6.8%), bemarituzumab in combination with FOLFOX in 77 patients (65.8%), and nintedanib in 32 patients (27.4%). 40 (34.2%) patients had prior trastuzumab therapy. Baseline performance status was good (ECOG 0–1) across studies. Median follow-up was 18 (10.9–28.3) months. Pooled overall response rate was 34% (95% CI, 7–79%; I² = 72.3%). Bemarituzumab significantly improved overall survival compared with placebo (HR 0.58), while median OS in single-arm cohorts was 8.2 months with pemigatinib and 14.2 months with nintedanib. Median progression-free survival ranged from 1.9 to 9.5 months across studies, with the longest PFS observed in the bemarituzumab cohort. Pooled overall mortality was 49% (95% CI, 12–87%; I² = 82%). Grade 3 or worse adverse events were variably reported and included neutropenia, stomatitis, hypertension, and corneal disorders. Notably, no grade 3 or worse adverse events, treatment-related mortality, or discontinuations were reported in the pemigatinib cohort (small, early-terminated study). Conclusions: FGFR-targeted therapies show activity in FGFR-altered esophagogastric cancers, especially with FGFR2b-directed monoclonal antibodies. Toxicities are manageable, but responses vary, highlighting the need for molecular selection. Larger trials are needed to identify patients most likely to benefit and optimal treatment sequencing.