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HER2-positive gastric/GEJ adenocarcinoma (~15-20%): trastuzumab + chemotherapy is standar...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDBMA-HER2-AMP-GASTRIC
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-GASTRIC
SourcesSRC-CIVIC SRC-ESMO-GASTRIC-2024 SRC-NCCN-GASTRIC-2025

Actionability Facts

BiomarkerBIO-HER2-SOLID
Variantamplification / overexpression — IHC 3+ or (IHC 2+ + ISH amplified, HER2/CEP17 ≥2.0); ~15-20% of gastric/GEJ adenocarcinoma
DiseaseDIS-GASTRIC
ESCAT tierIA
Recommended combinationstrastuzumab + fluoropyrimidine + platinum (1L per SRC-NCCN-GASTRIC-2025, SRC-ESMO-GASTRIC-2024), pembrolizumab + trastuzumab + fluoropyrimidine + platinum (1L HER2+ PD-L1 CPS ≥1 per SRC-NCCN-GASTRIC-2025), trastuzumab deruxtecan (2L+ post-trastuzumab progression per SRC-NCCN-GASTRIC-2025)
Contraindicated monotherapytrastuzumab monotherapy (combination with chemotherapy required for survival benefit)
Evidence summaryHER2-positive gastric/GEJ adenocarcinoma (~15-20%): trastuzumab + chemotherapy is standard 1L (ToGA Bang Lancet 2010 — mOS 13.8 vs 11.1 mo, HR 0.74). Pembrolizumab + trastuzumab + chemo is FDA-approved 1L for HER2-positive PD-L1 CPS ≥1 metastatic gastric/GEJ disease per SRC-NCCN-GASTRIC-2025, SRC-ESMO-GASTRIC-2024 (KEYNOTE-811). Trastuzumab deruxtecan (T-DXd) is FDA-approved 2L+ for HER2-positive (IHC 3+ or 2+) advanced gastric/GEJ adenocarcinoma based on DESTINY-Gastric01 (Shitara NEJM 2020 — ORR 51% vs 14% with chemotherapy).

Notes

ESCAT IA / OncoKB Level 1. Gastric HER2 scoring (Hofmann 2008) differs from breast: basolateral/lateral membranous staining ≥10% qualifies (cf. circumferential criterion in breast). HER2 testing recommended for all metastatic gastric/GEJ adenocarcinoma at diagnosis. Heterogeneity is significant: ≥4 endoscopic biopsies preferred. Source-gap: SRC-TOGA-BANG-2010, SRC-DESTINY-GASTRIC01, SRC-KEYNOTE-811 not yet ingested.

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