Abstract 1338P
Background
Human epidermal growth factor receptor 2 (HER2) gene has been identified as an oncogenic driver and drug target in non-small cell lung cancer (NSCLC). However, the status of tumor mutation burden (TMB) and programmed cell death-1 (PD-L1) expression in NSCLC patients harboring HER2 gene alterations have not been distinctly defined. The efficiency of immunotherapy in this population is still unclear. Here we described the prevalence of HER2 alterations in Chinese NSCLC patients and the status of TMB and PD-L1 in HER2-altered patients.
Methods
16,015 patients with NSCLC were enrolled in this study. Single nucleotide variant (SNV) and copy number variations (CNV) of HER2 were performed on tissue specimens or circulating tumor DNA by NGS. Only the pathogenic mutations and likely pathogenic mutations were analyzed. PD-L1 expression status was determined by immunohistochemistry using the Dako22C3 assay. The efficiency of immunotherapy was analyzed in a cohort of 63 patients with NSCLC from Zhejiang Cancer Hospital.
Results
Among 16,015 NSCLC patients, the total HER2 alterations frequency was 4.4%, including 3.0% of SNV and 1.7% of CNV. The prevalence of HER2 alterations in adenocarcinoma, squamous cell carcinoma and other subtypes of NSCLC was 4.8%, 2.5% and 3.2%, respectively. In our dataset, median TMB value was 6.1 mutations/MB (range, 0-383.5). The highest prevalence of median TMB fell in the HER2 CNV group (8.1 mutations/MB), followed by HER2 wild type (6.14 mutations/MB) and HER2 SNV (5.1 mutations/MB) groups. There was no significant difference in TMB among HER2 SNV, HER2 CNV and HER2 wild type groups. For PD-L1, compare to HER2 wild type groups, the positive rate of PD-L1 expression in HER2 variations was lower significantly (50.7% vs 33.6%, p<0.001). The positive rates of PD-L1 expression in HER2 SNV and HER2 CNV groups were 30.3% and 42.9%, respectively. In our cohort of NSCLC patients treated with immunotherapy, a shortened progression-free survival was observed in HER2 SNV compare to HER2 wild type (HR: 4.0, 95% CI 1.3-11.9, P = 0.014).
Conclusions
Our study showed the prevalence of HER2 alterations in Chinese NSCLC patients was 4.4%, and revealed the poor efficacy of immunotherapy in NSCLC patients harboring HER2 mutations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Zhejiang Cancer Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.