HER-2 Y772_A775dup

In 7 patients who received HER2-directed therapies, limited responses to afatinib (n=5), trastuzumab emtansine (n=3) and tucatinib (n=1) were observed and no responses were seen with immunotherapy monotherapy (n=2). The incidence of HER2-M+ is 3.1% in East Asian non-squamous NSCLC, with only 1/26 HER2ex20 overlapping with activating EGFR mutations. The clinical phenotype and genomic features of HER2ex20 tumours appear distinct from HER2other, the latter demonstrating higher TMB, co-occurring drivers and predominant non-ageing signature. The therapeutic implications of the genomic and clinical features of HER2-M+ warrant further investigation.)