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Poster session 01

81P - NF1 mutation as an indicator stratified patients benefit from immune checkpoint inhibitors in gastroesophageal cancers

Date

10 Sep 2022

Session

Poster session 01

Topics

Tumour Site

Oesophageal Cancer;  Gastric Cancer

Presenters

Haiping Xiao

Citation

Annals of Oncology (2022) 33 (suppl_7): S27-S54. 10.1016/annonc/annonc1037

Authors

H. Xiao1, L. Zhao2, M.Z. Xiao2, C. Qi2

Author affiliations

  • 1 Department Of Thoracic Surgery, First affiliated hospital of Guangdong College of Pharmacy, 510030 - Guangzhou/CN
  • 2 Medical, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing/CN
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Abstract 81P

Background

For locally advanced and metastatic gastroesophageal cancers, treatment options are limited. Preliminary data showed that ICIs in metastatic gastroesophageal cancer have demonstrated response rates of approximately 22%–27% for the subset of patients with PD-L1+ tumors (40%) and response rates of approximately 10%–17% for unselected patients. Therefore, investigating predictive biomarkers of ICIs is important to identify the target population that derives the best therapeutic benefit. Tumor suppressor gene neurofibromin 1 (NF1) encodes neurofibromin 1 protein, which negatively regulates the RAS/MAPK pathway. Targeting neurofibromin 1-regulated pathways offers potential therapeutic options for the treatment of tumors. However, its role in gastroesophageal cancer immunotherapy remains unknown. Here we aimed to demonstrate the association between NF1 and ICIs.

Methods

158 patients from two public immunotherapy cohorts (Janjigian 2017 and Samstein 2019 cohort) were included to analyze the association between NF1 gene mutation and efficacy of ICI therapy. Genomic, survival and mRNA data of gastroesophageal cancer patients from the Cancer Genome Atlas (TCGA) database was used to explore the potential mechanisms of anti-tumor immunity.

Results

In immunotherapy cohort, patients with NF1 mutation were significantly associated with better OS (HR = 0.23; P = 0.04) compared with those with wide-type. NF1 mutation were associated with increased TMB (P = 0.003). In TCGA, no association between NF1 mutation and OS was observed, suggesting that NF1 mutation may be a predictive but not a prognostic factor in ICI for gastroesophageal cancer. Based on CIBERSORT-inferred tumor infiltrating lymphocytes from TCGA, NF1 mutation was significantly associated with higher NK cells, and M1 macrophages. Moreover, NF1 mutation was associated with increased TMB (P = 0.02) in TCGA. In addition, GSEA analysis revealed that NF1 mutation was correlated with upregulated DDR signaling pathway in gastroesophageal cancer.

Conclusions

Our results demonstrated that NF1 mutation is an independent classifier that could stratify patients with gastroesophageal cancer for ICIs. The role of NF1 in immunotherapy is needed to be further studied.

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.

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