Before prescribing cetuximab for a patient with metastatic colorectal carcinoma, which molecular test result predicts lack of benefit and contraindicates its use?

• A HER2 amplification in the tumour
• B KRAS mutation in codon 12 or 13 of the tumour ✓
• C Loss of mismatch repair protein expression
• D BRAF V600E mutation in the tumour

Explanation

Cetuximab blocks the extracellular domain of EGFR, but downstream benefit requires an intact RAS signalling pathway. Activating KRAS mutations at codons 12 or 13 render the pathway constitutively active independent of EGFR, so anti-EGFR therapy produces no response. RAS testing is mandatory before use in metastatic colorectal cancer. BRAF mutation also predicts poor response but does not absolutely exclude benefit, HER2 amplification defines trastuzumab eligibility, and mismatch repair loss predicts checkpoint inhibitor responsiveness, not anti-EGFR failure.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.