Cetuximab is being considered for metastatic colorectal cancer. Before prescribing, tumour tissue testing shows no KRAS mutation in codons 12 and 13. During treatment the patient develops a prominent papulopustular facial rash. Which statement is correct?
- A Wild-type KRAS predicts benefit because the tumour retains upstream EGFR dependence, and severity of the skin rash correlates with response ✓
- B The rash is an allergic reaction mandating immediate permanent discontinuation
- C KRAS mutation status is irrelevant because cetuximab acts downstream at MEK
- D The rash indicates EGFR expression on normal keratinocytes and predicts treatment failure
Correct answer: A. Wild-type KRAS predicts benefit because the tumour retains upstream EGFR dependence, and severity of the skin rash correlates with response
Explanation
Cetuximab blocks EGFR, which drives signalling through RAS. Constitutively active mutant KRAS makes the pathway independent of EGFR, so only wild-type KRAS tumours respond. The acneiform rash arises from EGFR blockade in skin and hair follicles, and its severity paradoxically correlates with better tumour response, so it is managed supportively rather than by stopping the drug. Option C confuses cetuximab with MEK inhibitors such as trametinib.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.