Genomic alterations associated with resistance to anti-EGFR therapy, such as ERBB2 amplification, PIK3CA mutation, MAP2K1 mutation, and KRAS amplification, were identified in patients with left-sided RAS/BRAF wild-type mucinous metastatic colorectal cancer. However, patients with left-sided RAS/BARF wild-type mucinous colorectal cancer treated with first-line anti-EGFR therapy had significantly worse progression-free survival (4 vs 6.5 months, hazard ratio [HR] = 5.3, 95% confidence interval [CI] 1.3-21.7, P = .01) than patients treated with the first-line vascular endothelial growth factor A antibody, bevacizumab. Anti-EGFR therapy was associated with limited responses and a short PFS across all lines of therapy in 12 patients with left-sided RAS/BRAF wild-type mucinous colorectal cancer. Among the 20 patients with left-sided RAS/BRAF wild-type mucinous metastatic colorectal cancer, 12 patients were given panitumumab...The median PFS in patients treated with first-line panitumumab-based therapy was 4 months versus 6.5 months with bevacizumab-based therapy (P = .01, HR = 5.3, 95% CI 1.3-21.7, P = .01).