Elevated PD-L1 Expression and Microsatellite Instability in Elderly Patients With Gastric Cancer

Tien Hua Chen, Ming Huang Chen, Yi Ping Hung, Nai Jung Chiang, Kuo Hung Huang, Yi Hsiang Lin, Ryan Weihsiang Lin, Yee Chao, Anna Fen Yau Li, Hung Yuan Yu, Hsuen En Hwang, Yi Chen Yeh, Yu Chao Wang*, Wen Liang Fang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P=0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P=0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P=0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P=0.041; combined positive score ≥1: 38.1%/21.5%, P<0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.

Original languageEnglish
Pages (from-to)111-119
Number of pages9
JournalJournal of Immunotherapy
Volume46
Issue number3
DOIs
StatePublished - 1 Apr 2023

Keywords

  • gastric cancer
  • immunotherapy
  • microsatellite instability
  • programmed cell death-ligand 1
  • tumor mutation burden

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