Before starting an anti-EGFR monoclonal antibody (cetuximab or panitumumab) for metastatic colorectal carcinoma, testing for which molecular alteration is mandatory because its presence predicts complete lack of benefit?
- A Microsatellite instability
- B BRAF V600E mutation
- C KRAS mutation in codons 12 and 13 ✓
- D HER2 amplification
Correct answer: C. KRAS mutation in codons 12 and 13
Explanation
Anti-EGFR antibodies act upstream, so they are ineffective when the downstream RAS pathway is constitutively activated. Mutations in KRAS exon 2 (codons 12 and 13), and later also NRAS and extended RAS mutations, predict resistance, and guidelines require RAS wild-type status before prescribing cetuximab or panitumumab. BRAF V600E mutation confers a poor prognosis and relative resistance but does not absolutely abolish benefit the way RAS mutation does, making it the tempting but incorrect distractor.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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