HER2 Mutations: TKIs Take the Wheel

Switching lanes to ERBB2-activating mutations, the faculty outline why exon 20 inserts scream for tucatinib (or poziotinib) rather than trastuzumab. Down-regulating surface HER2 may boost TKI potency, explaining the combo data, but they doubt an antibody alone adds much when overexpression is absent. Lung-cancer data for T-DXd in mutant tumors likely reflect low-level protein that happens to be druggable, not necessarily synergy with topoisomerase payloads.