Abstract 5003
Background
Immunotherapy has been proven to be effective in gastric cancer (GC) patients. But the efficacy of immunotherapy for HER2 positive GC has not been defined. Tumor mutation burden (TMB) has been considered as predictive biomarkers of immunotherapy. However, the association between HER2 alterations and TMB in GC is still unclear. We therefore analyzed the associated between HER2 alterations and TMB in Chinese patients with GC.
Methods
Genomic profiling of DNA from fresh or FFPE tumor tissue of 163 Chinese GC was performed using next-generation sequencing on 381 cancer associated genes in 3D Medicines laboratory. Whole-exome sequencing and Genomic Identification of Significant Targets in Cancer (GISTIC) data of 435 GC from The Cancer Genome Altas (TCGA) were also analyzed to evaluate the association between HER2 alterations with TMB. TMB was defined as number of somatic non-synonymous mutations in coding region. HER2 amplification in TCGA was defined as “2” derived from the copy-number analysis algorithms GISTIC.
Results
HER2 alterations including amplification, missense and fusion were present in 11.0% (18/163) of Chinese cohort and 17.0% (74/435) of TCGA cohort. 5.5% (9/163) of Chinese cohort and 14.3% (62/435) of TCGA cohort harbored HER2 amplification. Higher TMB level was observed in patients carrying any HER2 alterations (P = 0.004) in Chinese cohort, but the association was not found in TCGA cohort (P = 0.379). Prognosis analysis was also performed on patients in TCGA cohort. HER2 status was not an independent risk factors affecting disease free survival (HR, 1.007; 95%CI 0.60-1.69; P = 0.979) or overall survival (HR, 0.828; 95%CI 0.56-1.24; P = 0.357). Higher TMB level was associated with significantly better disease free survival (median, 43.04 vs. 25.53 months; HR, 0.685; 95%CI 0.47-1.00; P = 0.048) and a borderline improvement in overall survival (median, 42.51 vs. 25.69 months; HR, 0.75; 95%CI 0.56-1.02; P = 0.070).
Conclusions
HER2 alterations are associated with higher TMB in Chinese GC patients, but not in patients from TCGA. Chinese GC patients may exhibit distinct characteristics. Further studies are warranted to evaluate the efficacy of immunotherapy in GC patients with HER2 alterations.
Clinical trial identification
Legal entity responsible for the study
Yanhong Gu.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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