HER2-targeted therapy should be shifted towards an earlier line for patients with anti-EGFR-therapy naïve, HER2-amplified metastatic colorectal cancer

Bregni and colleagues suggested potential clinical utility for anti-epidermal growth factor receptor (EGFR) therapy in HER2-amplified metastatic colorectal cancer (mCRC), based on re-evaluation of the HERACLES study in which 14/26 patients with HER2-amplified mCRC had stable disease ≥6 months with that treatment.1 However, it is difficult to prove the presence of a survival benefit from anti-EGFR therapy due to the lack of a control. We previously reported progression-free survival (PFS) with anti-EGFR therapy was significantly shorter in patients with HER2-amplified mCRC versus those with wild-type RAS/BRAF (median PFS 2.6 vs 6.0 months; HR 3.89; 95% CI 1.49 to 10.18) and similar to those with mutant RAS (median PFS 2.6 vs 2.2 months; HR 1.05; 95% CI 0.38 to 2.92).