Real-world frequency of non-small cell lung cancer with ERBB2 exon 20 insertion (Exon20ins) mutations by site of insertion.

e15026 Background: ERBB2 Exon20ins mutations are in-frame insertions or duplications clustered around 2 key regions of Exon 20: the α-C helix (amino acid [AA] 770-774), the loop following the α-C helix (amino acid [AA] 775-783). The site of insertion can influence the outcome to selective EGFR/ERBB2 tyrosine kinase inhibitor therapy; ERBB2 exon 20 insertion mutation remains an unmet clinical need. The next-generation sequencing technology is a powerful tool to investigate the detailed ERBB2 mutations sites. Methods: We used real-world HaploX genomic data from patients (pts) with non-small cell lung cancer (NSCLC) to determine the frequency of ERBB2 Exon20ins mutations by site of insertion.The tumor tissue or serial blood sample was collected for each individual and the next-generation sequencing was performed using customized target captured HapOncoCDx panels. Results: From HaploX genomic data, 284/18205 pts (1.56%) with NSCLC had ERBB2 Exon20ins mutations: 72.2% were located in the helix, 27.8% in the loop (Table). The top 3 most frequent sites of insertion were Y772_A775dup (71.5%), G776delinsVC (11.3%), and G778_P780dup (6.0%). Conclusions: This real-world databases identified the helix as the most frequent insertion region of Exon 20 (∼72%). Exon20ins mutations were found less frequently in the loop (∼28%).[Table: see text]