FGFR2b as a Therapeutic Biomarker in Gastric Cancer: Lessons from Bemarituzumab and Implications for Next-Generation...

FGFR2b is an appealing therapeutic biomarker in gastric and gastroesophageal junction adenocarcinoma, but first-line bemarituzumab development ended despite a statistically positive FORTITUDE-101 primary overall-survival analysis. This review uses the bemarituzumab programme to examine what a clinically useful FGFR2b biomarker must capture and how those requirements change across therapeutic modalities.

FGFR2b protein overexpression and FGFR2 genomic alteration identify related but non-equivalent populations. Assay threshold, specimen age and spatial heterogeneity affect apparent expression. Within both FIGHT and FORTITUDE-101, OS hazard-ratio estimates moved toward the null at later data cutoffs, although results should not be interpreted across trials as a single trend. A phase 3 trial on a nivolumab-containing backbone was stopped for inadequate efficacy according to sponsor communications. Neither phase 3 study has yet been fully reported in a peer-reviewed publication. Emerging FGFR2-directed agents may require modality-specific biomarkers beyond the original bemarituzumab staining threshold. Prospective development should evaluate modality-matched biomarkers: accessible surface protein and spatial distribution for antibodies, activating genomic changes for kinase inhibitors, and antigen density, internalisation, trafficking and payload sensitivity for antibody-drug conjugates. These remain research priorities rather than validated patient-level treatment rules.