La sobreexpresión de la proteína FGFR2b (IHC 2+/3+ membranosa en ≥10% de las células tumorales) identifica un...
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| ID | BMA-FGFR2B-MEMBRANE-GASTRIC |
|---|---|
| Tipo | Relevancia terapéutica |
| Situación | reviewed 2026-05-07 | pending_clinical_signoff | actionability review required |
| Enfermedades | DIS-GASTRIC |
| Fuentes | SRC-ESMO-GASTRIC-2024 SRC-FORTITUDE-101 SRC-NCCN-GASTRIC-2025 |
Hechos relativos a la posibilidad de adoptar medidas
| Biomarcador | BIO-FGFR2B-IHC |
|---|---|
| Variante | FGFR2b 2+/3+ coloración membranosa en ≥10% de las células tumorales por IHC selectivo de isóformo IIIb (FORTITUDE-101 / umbral de elegibilidad de lucha) |
| Enfermedad | DIS-GASTRIC |
| El nivel de ESCAT | IIA |
| Combinaciones recomendadas | bemarituzumab + mFOLFOX6 (1L FGFR2b-IHC 2+/3+ ≥10% — régimen de fase 2 de lucha; confirmación FORTITUDE-101) |
| Monoterapia contraindicada | bemarituzumab en monoterapia (no hay datos de registro; espina dorsal de quimioterapia requerido por diseños de lucha / Fortitude-101) |
| Resumen de las pruebas | FGFR2b protein overexpression (IHC 2+/3+ membranous in ≥10% of tumor cells) identifies a ~30% subset of HER2-negative metastatic gastric / GEJ adenocarcinoma sensitive to bemarituzumab — anti-FGFR2b chimeric IgG1 monoclonal antibody with afucosylated Fc enhancing ADCC. FIGHT phase 2 (Wainberg et al. Lancet Oncol 2022): bemarituzumab + mFOLFOX6 vs placebo + mFOLFOX6 in FGFR2b-overexpressing 1L gastric — mPFS 9.5 vs 7.4 mo (HR 0.68), mOS 19.2 vs 13.5 mo (HR 0.60); benefit greater at higher FGFR2b cutoffs (≥10% vs all-comer). Phase 3 confirmatory trial FORTITUDE-101 (interim data — full readout pending; source stub flagged). Distinct from FGFR2 gene amplification (covered by BMA-FGFR2-AMP-GASTRIC) — IHC selects on protein expression of the IIIb isoform regardless of underlying gene amp status. Adverse-event profile dominated by ocular toxicity (corneal events ~70% any-grade, ~25% grade ≥3) — mandatory baseline + serial slit-lamp ophthalmologic exams. |
Notas
ESCAT IIA — phase 2 randomized data (FIGHT) supports the cell; confidence will upgrade to IA upon full FORTITUDE-101 publication. CITATION GAP: SRC-FORTITUDE-101 is currently a TODO-stub (legal review pending, title placeholder). Cited as-is per chunk-spec instruction; upgrade is a separate housekeeping task. Distinguishing this BMA from BMA-FGFR2-AMP-GASTRIC (gene amplification → off-label TKI / basket trial activity) — the protein-IHC and gene-amp tests overlap in ~50% of cases but each captures a distinct subset (FIGHT data, Wainberg Lancet Oncol 2022). Hierarchy when multiple biomarkers co-positive: HER2+ (TOGA / KEYNOTE-811) > MSI-H (KEYNOTE-859) > CLDN18.2+ (SPOTLIGHT / GLOW) > FGFR2b+ (FIGHT / FORTITUDE-101). Ocular toxicity is the dose-defining AE — protocol-driven ophthalmology pre-treatment + ongoing slit-lamp surveillance.
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