dMMR/MSI-H is a key molecular subtype of gastric cancer, found in 8-22% of cases. It is typically associated with older age, female sex, distal tumor location, and intestinal histology (Lauren classification). While this subtype predicts better survival in locally advanced disease, its prognostic role in metastatic settings is less clear.
Notably, dMMR/MSI-H tumors are often resistant to conventional chemotherapy. Conversely, they demonstrate exceptional sensitivity to immunotherapy. This has led to effective strategies using immune checkpoint inhibitors, either alone or combined with chemotherapy, in both neoadjuvant and advanced disease settings.
However, key challenges remain. Prospective data are largely from Western populations, leaving the efficacy in Asian patients-who bear a high disease burden-less defined. Furthermore, about half of dMMR/MSI-H patients exhibit primary or acquired resistance to immunotherapy. A deeper understanding of the tumor-immune dynamics during treatment is crucial to uncover resistance mechanisms and improve patient outcomes.
Male or female, aged 18 to 85 years.
Histologically confirmed gastric cancer or adenocarcinoma of the esophagogastric junction (only Siewert types II and III are included).
dMMR status confirmed by immunohistochemistry (IHC) or MSI-H status confirmed by PCR/NGS.
Willing to receive treatment with immune checkpoint inhibitors (including, but not limited to, various PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors, PD-1/CTLA-4 bispecific antibodies, etc.), which may be combined with or without standard chemotherapy regimens for gastric cancer.
Tumor histology other than adenocarcinoma, such as squamous cell carcinoma, neuroendocrine carcinoma, etc.
Presence of central nervous system metastases and/or leptomeningeal carcinomatosis.
Prior antitumor therapy directed at the current gastric cancer (excluding palliative gastrointestinal bypass surgery performed to relieve obstructive symptoms).
Single group
Immunotherapy
DrugDrug: Immune checkpoint inhibitors (ICIs), specifically PD-1 antibodies, PD-L1 antibodies, PD-1/CTLA-4 bispecific antibodies, or PD-1/CTLA-4 combination therapy. Regimen: 4 treatment cycles.
Induction chemotherapy
DrugDrug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m\^2
D2 radical gastrectomy
Procedure/SurgeryCurative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.
Rate of pathological complete response
The proportion of subjects exhibiting no residual tumor cells in the surgical specimen and the absence of positive lymph nodes (i.e., a pathological stage of ypT0N0).
Major Pathological Response Rate
The proportion of subjects with residual viable tumor cells accounting for \<10% of the surgical specimen from the primary tumor site.
ypN stage
Lymph-node status after neoadjuvant therapy (ypN stage) will be assessed according to the American Joint Committee on Cancer (AJCC) 8th edition staging system.
R0 resection rate
The proportion of patients who undergo surgery with microscopically negative resection margins.
Event-free Survival
The time from the subject's enrollment until disease progression, disease recurrence, or death from any cause.
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