Before starting an anti-EGFR monoclonal antibody such as cetuximab in metastatic colorectal cancer, testing for which biomarker is mandatory because its mutation predicts complete lack of benefit?
- A HER2 amplification status
- B KRAS codon 12/13 mutation status ✓
- C Microsatellite instability status
- D BCR-ABL fusion transcript level
Correct answer: B. KRAS codon 12/13 mutation status
Explanation
Anti-EGFR antibodies act upstream of RAS signalling, so activating mutations in KRAS exon 2 (codons 12 and 13) drive the pathway independently of EGFR and render cetuximab and panitumumab ineffective. Guidelines require tumour tissue to be RAS wild type before use. Microsatellite instability predicts response to PD-1 blockade, not anti-EGFR therapy, and HER2 amplification is relevant in breast and gastric cancer.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.