Abstract 2375: Comprehensive analysis of immunotherapy-related biomarkers in Chinese patients with gastric adenocarcinoma
Authors: Qun Zhao, Yuntong Guo, XiaoLong Cui, LiangBiao Peng, Junying Li, Fei Wang, Lin Zhang
Journal: Cancer Research (2021)

Abstract Background: Gastric adenocarcinoma (GAC) is a deadly disease in need for new therapies. Recently, the most exciting developments in oncology are immune checkpoint inhibitors (ICIs) such as inhibitors of programmed cell death protein 1 (PD-1) which has shown response rates of 11-16% in unselected GAC patients. This study aimed to characterize the distributions of immunotherapy-related biomarkers in Chinese patients with gastric adenocarcinoma. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples and matched peripheral blood samples of 497 Chinese gastric adenocarcinoma patients were collected for YuansuTM NGS-panel assay (OrigiMed, Shanghai). Genomic alterations (GAs) including single nucleotide variations, short and long insertions/deletions, copy number variations, and gene rearrangements were assessed. Microsatellite instability (MSI), PD-L1 expression and tumor mutational burden (TMB) were assessed in 467(94%), 208(42%) and 467(94%) patients, respectively. Results: There were 334 males (67.2%) and 163 females (32.8%) with a median age of 60 (range 23-87) years in this cohort, including 440 primary tumors and 57 metastases. MSI-H was detected in 39 samples (7.8%). The rate of MSI-H in the ACVR2A mutation group was significantly higher than that in the ACVR2A wild-type group (82.1% vs 17.9%, p&amp;lt;0.001). In addition, we found that patients with mutations of K437Rfs*5 (54.1%) or D96Tfs*54 (11.4%) of ACVR2A were all MSI-H. The frequency of ERBB2 amplification was 7.5%, which was mutually exclusive to MSI-H. PD-L1 expression levels by CPS of negative, 1-9 and ≥10 were 54%, 33% and 13%, respectively. The median value of TMB was 6.2 (0-99.3) muts/Mb and TMB ≥10 muts/Mb was seen in 27.4% tumors. The patients with ACVR2A mutations had a significantly higher TMB (ACVR2A: 5.7 vs 2.6 muts/Mb, respectively, p &amp;lt; 0.01). In addition, the biomarkers associated with hyperprogression (HP) to immune checkpoint inhibitors (ICIs) included 11q13 amp, MDM2/MDM4 amp, and CDKN2A/B gene loss, which were identified in 4%, 2% and 2% of patients, respectively. Conclusions: We analyzed the distribution of microsatellite status, PD-L1 expression and TMB in Chinese patients with GAC. Interestingly, our data showed that mutated ACVR2A was significantly associated with MSI-H and TMB-H. In addition, approximately 8% of patients were identified harboring hyperprogression-related gene alterations. Therefore, the application of comprehensive genomic profiling might be necessary in guiding ICI treatments in GAC. Citation Format: Qun Zhao, Yuntong Guo, XiaoLong Cui, LiangBiao Peng, Junying Li, Fei Wang, Lin Zhang. Comprehensive analysis of immunotherapy-related biomarkers in Chinese patients with gastric adenocarcinoma [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 2375.