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Abstract
ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 insertion Y772_A775dupYVMA was the most frequent alteration (58% vs 41.6% in the Chinese vs the US), followed by G776delinsVC/LC/VV/IC (10.7% vs 9.7%), and S310X (10.5% vs 15.4%). EGFR ex20 insertions were identified in the A767-V774 region, whereas ERBB2 ex20 insertions were observed in the Y772-P780 region. Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.
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1 The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Imaging Physics, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)
2 The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)
3 Guardant Health, Redwood City, USA (GRID:grid.511203.4)
4 Geneplus-Beijing, Beijing, China (GRID:grid.512993.5)
5 Chinese Academy of Medical Sciences and Peking Union Medical College, Department of International Medical Services, Peking Union Medical College Hospital, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839)
6 Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839)
7 The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Genomic Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)