The Characteristics Of Erbb2 Exon 20 Insertion In A Large Cohort Of Chinese Nsclc Patients.

Abstract Background: ERBB2 mutations, especially exon 20 insertion (ERBB2ex20ins) had been extensively reported in NSCLC as classical driver factors. Previous researches indicate that NSCLC pts with ERBB2ex20ins are drug-resistant to afatinib, gefitinib and erlotinib. Up to now, approvals of targeted therapy of ERBB2ex20ins are still in process. Therefore, the objective of this study is to discover the features of ERBB2ex20ins in Chinese NSCLC patients, which could lead to more effective and personalized diagnosis and treatment. Methods: 20656 Chinese NSCLC cases who had undergone molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA) certified genomics laboratory in China between January 2017 to May 2020 were screened for our study. Some patients' clinical characteristics and treatment history were retrieved from the database for further evaluation. Results: 11492 males and 9134 females were included in our cohort. ERBB2 gene mutation rate was 5.94% (1226/20656). Among them, 290 patients (1.4%), including 114 males and 176 females, harbored with ERBB2ex20ins, which include with p. Tyr772_Ala775dup (84.56%), p.Gly778_Pro780dup (10.74%), p.Ala775_Gly776insLeu(1.01%), p.Ala775_Gly776insVal(1.01%) and others(2.68%). Additionally, ERBB2ex20ins occurred more frequently in female patients (61% vs 39%, p<0.005, fisher exact test), and had a relatively young age (p<0.005, wilcoxon test) compared with others. Moreover co-variations of 290 pts are occurring with EGFR(4, 1.38%), KRAS(3, 1.03%), TP53(156, 53.79%), ERBB2 amp(21, 7.24%), MET amp (2, 0.69%), ALK amp (1, 0.34%) and RET fusion (1, 0.34%). Besides, a relatively lower TMB (p<0.005, wilcoxon test) is shown on the patients with ERBB2ex20ins. We followed up 5 patients with ERBB2ex20ins mutations, who were all insensitive to traditional radiotherapy and chemotherapy and had poor prognosis with short PFS (1.5-12.4 months) and short OS (3.9-13.7 months). Conclusion: Our results showed that the ERBB2ex20ins mutation tended to occur in younger, female patients. Additionally, ERBB2ex20ins mutated samples exhibited lower levels of TMB compared to wildtype tumors, which may not benefit from anti-PD1 treatment. We also found patients with ERBB2ex20ins mutation have been associated with short PFS and short OS. The detail mechanism of resistance and appropriate therapeutic strategies remain to be further study. Citation Format: Danhua Wang, Hongling Yuan, Honglin Zhu. The characteristics of ERBB2 exon 20 insertion in a large cohort of Chinese NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2313.