HER2-amplified metastatic colorectal cancer (~3-5% in RAS/BRAF-WT population): tucatinib...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-HER2-AMP-CRC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-CRC |
| Sources | SRC-CIVIC SRC-ESMO-COLON-2024 SRC-NCCN-COLON-2025 |
Actionability Facts
| Biomarker | BIO-HER2-SOLID |
|---|---|
| Variant | amplification / overexpression — IHC 3+ or (IHC 2+ + ISH amplified, HER2/CEP17 ≥2.0); ~3-5% of metastatic colorectal cancer (RAS/BRAF-WT) |
| Disease | DIS-CRC |
| ESCAT tier | IB |
| Recommended combinations | tucatinib + trastuzumab (2L+ HER2+ RAS-WT mCRC per SRC-NCCN-COLON-2025), trastuzumab deruxtecan (2L+ HER2+ mCRC per SRC-NCCN-COLON-2025), trastuzumab + lapatinib (alternative per HERACLES, listed in SRC-NCCN-COLON-2025) |
| Contraindicated monotherapy | HER2-directed therapy in RAS-mutated mCRC (RAS mutation drives downstream resistance per SRC-NCCN-COLON-2025), trastuzumab monotherapy |
| Evidence summary | HER2-amplified metastatic colorectal cancer (~3-5% in RAS/BRAF-WT population): tucatinib + trastuzumab is FDA-approved 2L+ for HER2- positive RAS-WT mCRC based on MOUNTAINEER (Strickler Lancet Oncol 2023 — ORR 38%, mDOR 12 mo) per SRC-NCCN-COLON-2025. Trastuzumab deruxtecan also has activity (DESTINY-CRC01 Siena Lancet Oncol 2021 — ORR 45% in HER2 IHC 3+ RAS-WT) and tumor-agnostic FDA approval (2024) for HER2-positive solid tumors that have progressed on prior therapy. Older trastuzumab + lapatinib (HERACLES) is referenced as alternative. RAS-mutant tumors should not receive HER2-directed therapy in 2L because RAS-driven resistance is well-documented per SRC-NCCN-COLON-2025. |
Notes
ESCAT IB / OncoKB Level 2 (initially Level 2A in CRC pre-MOUNTAINEER; Level 1 tumor-agnostic for T-DXd 2024). HER2 testing recommended for metastatic CRC with RAS/BRAF-WT genotype per SRC-NCCN-COLON-2025. RAS mutation = exclusion criterion for anti-HER2 therapy. Source-gap: SRC-MOUNTAINEER-STRICKLER-2023, SRC-DESTINY-CRC01, SRC-HERACLES not yet ingested.
Used By
No reverse references found in the YAML corpus.