Impact of ARID1A mutation in nivolumab treatment for gastric cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18084
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Hagi Takaomi 大阪大学, 医学部附属病院, 医員 (50804465)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: nivolumab / 胃癌 / 免疫チェックポイント阻害剤 / PD-L1 / Mismatch repair蛋白 / ARID1A

Outline of Final Research Achievements

In this study, tissue specimens of patients with gastric cancer and treated with nivolumab as third-line or higher therapy were collected. PD-L1 expression, mismatch repair (MMR) status, and ARID1A expression were analyzed by immunohistochemistry. Associations with tumor-response rate and survival were assessed.
The response rate was 17.5%. The response rate was significantly higher in patients with performance status (PS) 0-1 (P = 0.026), non-peritoneal metastasis (P =0.021), PD-L1 TPS ≧1 (P = 0.012), CPS ≧5 (P = 0.007) or ≧10 (P < 0.001) or MMR deficiency (P < 0.001). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P < 0.001), peritoneal metastasis (P = 0.004) and CRP (P < 0.001).

Free Research Field

胃癌治療

Academic Significance and Societal Importance of the Research Achievements

胃癌のnivolumab治療の効果効果予測に有効なバイオマーカーは見つかっておらず、これらの探索が重要な課題となっている。今回の研究により、胃癌患者の腫瘍組織の免疫染色におけるPD-L1発現(CPS≧10)やMMR deficiencyが治療効果予測に有用な可能性が示唆された。nivolumab治療の選択時における新たな指標となる可能性が考えられる。