Abstract 466P
Background
The overexpression of HER2 has proved an effective target in several other malignancies such as gastric cancer and breast cancer, and this inspired the exploration of HER2-targetting therapy in colorectal cancer (CRC) since a certain proportion of CRCs carried the HER2 oncogene alteration in CRC. Recently published results show promising evidence suggesting HER2-targetting therapy may have a potential efficacy in the treatment of HER2-positive metastatic CRC. However, it is necessary to clarify the data on alterations in HER2 in Chinese CRC patients before conducting larger clinical trials.
Methods
The formalin-fixed paraffin-embedded specimens of Chinese CRC patients (n=5756) who underwent next-generation sequencing (NGS) from 2017 to 2021 in 3DMed Clinical Laboratory Inc. were included. Tumor mutational burden (TMB) was measured by a 733 gene panel. PD-L1 expression detected by using Dako PD-L1 IHC 22C3 pharmDx, T.
Results
8.76% (507/5786) CRC patients carry alteration in gene HER2, and 5.03% (291/5786) patients were pathogenic mutations, the others were benign, likely benign, or a variant of unknown clinical significance. Among all HER2 alterations, copy number variants (CNV) were less frequent than single nucleotide variants (SNV) (3.04% vs 5.69%), while in pathogenic mutations they were 3.01%, 2.28% for CNV and SNV, respectively, and 0.26% were CNV accompanied by SNV. In addition, there were 47.48% patients with KRAS mutation, however, only 1.52% were co-mutation with HER2 alterations. TMB level and PD-L1 expression level, and proportion of MSI-H were compared among groups with CNV, SNV, and CNV accompanied by SNV, and no significant difference was found among these groups; however, TMB level was significantly higher in SNV than in CNV group (p<0.001). Further analysis revealed that the median TMB level, proportion of MSI-H were higher in group of SNV than CNV (48% vs 0%).
Conclusions
Clarification of data in this area will lead to the development of treatment options for HER2. In addition, for the different alterations of HER2 in CRC patients, the decision on whether to choose immunotherapy should be treated differently.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.