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KRAS G12C in mCRC (~3-4%): single-agent KRASG12C inhibitors insufficient (intrinsic EGFR...

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

IDBMA-KRAS-G12C-CRC
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-CRC
SourcesSRC-CIVIC SRC-ESMO-COLON-2024 SRC-NCCN-COLON-2025

Actionability Facts

BiomarkerBIO-KRAS-G12C
VariantG12C
DiseaseDIS-CRC
ESCAT tierIB
Recommended combinationsadagrasib + cetuximab, sotorasib + panitumumab
Contraindicated monotherapyKRASG12C inhibitor monotherapy in CRC (analogous to BRAFi-monotherapy failure: EGFR-mediated reactivation)
Evidence summaryKRAS G12C in mCRC (~3-4%): single-agent KRASG12C inhibitors insufficient (intrinsic EGFR feedback). Combination adagrasib + cetuximab (KRYSTAL-1, Yaeger et al. NEJM 2023) ORR 46%, PFS 6.9 mo. Sotorasib + panitumumab (CodeBreaK 300, Fakih et al. NEJM 2023) ORR 26% vs investigator's choice. Both FDA-approved 2024.

Notes

ESCAT IB. OncoKB Level 1. Combo with anti-EGFR antibody is mandatory. Frontline still FOLFOX/FOLFIRI ± bev.

Used By

No reverse references found in the YAML corpus.