pairingsPairing
Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC
In bowel cancers that start on the left and have normal RAS and BRAF genes, adding an EGFR antibody to chemotherapy gives the longest survival seen in first-line trials.
PARADIGM: OS 37.9 months with panitumumab + mFOLFOX6 in left-sided RAS wild-type disease. FIRE-3 and CALGB 80405 subgroups agree. Right-sided or RAS/BRAF-mutant tumours should get bevacizumab instead. Anti-EGFR rechallenge after a chemotherapy-free interval, guided by ctDNA showing RAS/EGFR clones have receded (CHRONOS), is an emerging strategy.
Rationale
Left-sided tumours are EGFR-ligand dependent and RAS wild-type; right-sided tumours carry BRAF, dMMR, and other resistance biology.
Evidence
Phase 3 (PARADIGM) with OS benefit; multiple consistent retrospective analyses.