Abstract: Objective To assess the efficacy and safety of immunotherapy, plus anti-angiogenic drug and chemotherapy for advanced or metastatic gastric cancer (GC), and to explore the potential biomarkers associated with response. Methods The clinical data of 23 elderly patients with human epidermal growth factor receptor 2(HER2)-negative advanced or metastatic GC who received immune checkpoint inhibitor plus anti-angiogenic drug and chemotherapy were retrospectively analyzed. The effectiveness of the conversion therapy was evaluated by the proportion of the patients who were considered operable by a gastric surgeon after postoperative pathological assessment and multidisciplinary team ( including the departments of radiology, gastric surgery, and oncology) consultation. The patients were stratified by biomarkers using next generation sequencing (NGS) and multiple immunofluorescence (mIF). Results The Objective response rate was 78.3%(95%CI:56.3%－92.5%) and disease control rate was 87.0%(95%CI: 66.4%－97.2%). Eight patients (34.8%) achieved conversion therapy and R0 resection rate was 87.5% (7/8). Furthermore, seven patients (87.5%) responded to the treatment, with 1 case of pathological complete response and 6 cases of major pathological response. The patients responding to combination therapy had significantly higher proportion of CD8⁺ T cell in tumor center and invasive margin before treatment (P<0.05), and the density and fraction of CD8⁺ T cells significantly increased after combination treatment in the invasive margin (P<0.05). Conclusions Immunotherapy plus anti-angiogenic drug and chemotherapy is a promising treatment strategy for advanced and metastatic GC in the elderly patients. Tumor infiltration of CD8⁺ T cells may serve as potential predictive biomarker.

Key words: gastric cancer, PD-1 monoclonal antibody, anti-angiogenesis, conversion therapy, tumor immune microenvironment