老年晚期胃癌转化治疗中PD-1单抗联合化疗与抗血管生成药物的疗效及生物标记物分析

doi:10.3969/j.issn.1003-9198.2025.08.010

摘要/Abstract

摘要： 目的评价PD-1单抗联合化疗和抗血管生成药物对不可切除进展期及晚期老年胃癌病人的有效性和安全性,并探索与治疗响应相关的潜在生物标志物。方法回顾性分析23例接受PD-1单抗和抗血管生成药物联合化疗的人表皮生长因子受体2(HER2)阴性的进展期或晚期老年胃癌病人的临床资料。通过术后病理评估和MDT多学科(影像科、胃外科、肿瘤科)会诊后,以胃外科医生认为可以手术的比例评价转化治疗有效性。通过二代测序(NGS)和多重免疫荧光(mIF)对病人进行生物标记物分层分析。结果所有对象客观缓解率(ORR)达到78.3% (95% CI:56.3%~92.5%),疾病控制率(DCR)达到87.0% (95% CI:66.4%~97.2%)。8例(34.8%)达到转化治疗,R0切除率为87.5%(7/8)。其中7例(87.5%)对治疗响应良好, 1例达到病理完全缓解(pCR),6例达到主要病理缓解(MPR)。响应组联合治疗前肿瘤中心和浸润边缘的CD8⁺ T细胞比例显著高于非响应组(P<0.05),并且在联合治疗后浸润边缘的CD8⁺ T细胞的密度和比例也显著增加(P<0.05)。结论 PD-1单抗联合化疗和抗血管生成药物对于进展期及晚期老年胃癌病人是一种有前景的治疗方案,而CD8⁺ T 细胞的浸润也可以作为一种潜在的预测生物标志物。

关键词: 胃癌, PD-1单抗, 抗血管生成, 转化治疗, 肿瘤免疫微环境

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

中图分类号:

R735.2

赵坤, 王伟, 徐同鹏. 老年晚期胃癌转化治疗中PD-1单抗联合化疗与抗血管生成药物的疗效及生物标记物分析[J]. 实用老年医学, 2025, 39(8): 802-807.

ZHAO Kun, WANG Wei, XU Tongpeng. Efficacy and biomarker analysis of PD-1 monoclonal antibody combined with chemotherapy and anti-angiogenic drugs in conversion therapy for elderly patients with advanced gastric cancer[J]. Practical Geriatrics, 2025, 39(8): 802-807.

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