Xu Tongpeng, Wang Wenjie, Bao Ruikang, Xia Xihua, Zhang Junling, Huang Mengli, Chen Xiaofeng, Wang Rong, Zhang Hao, Liu Xisheng, Li Qiong, Shu Yongqian
Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Gusu School, Nanjing Medical University, Suzhou, China.
J Gastrointest Oncol. 2023 Feb 28;14(1):175-186. doi: 10.21037/jgo-23-73.
Immunotherapy plus chemotherapy have been confirmed to be effective in treating advanced or metastatic gastric cancer (GC). Anti- programmed death-1 (PD-1) plus antiangiogenic agents have shown promising activity and tolerant toxicity in subsequent therapy of late-stage gastric cancer. The aim of this study was to assess the efficacy and safety of anti-PD-1 plus anti-angiogenic agents and chemotherapy in advanced or metastatic GC and to explore the potential biomarkers associated with response.
We retrospectively reviewed thirty human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic GC patients who received PD-1 plus anti-angiogenic drugs and chemotherapy. Conversion therapy was defined when the patients could undergo resection post combination therapy. Clinical data were retrieved from medical records. We conducted exploratory biomarker analysis of baseline gene mutations and tumor mutation burden (TMB) using the next-generation sequencing (NGS), PD-L1 by immunohistochemistry (IHC), and the tumor immune microenvironment (TIME) by multiplex immunofluorescence.
A total of 30 patients received anti-PD-1plus anti-angiogenic drugs and chemotherapy during the study period. The objective response rate (ORR) was 76.7% [95% confidence interval (CI): 57.7-90.1%] and disease control rate (DCR) was 86.7% (95% CI: 69.3-96.2%). A total of 11 patients (36.7%) achieved conversion therapy and underwent surgery. The R0 resection rate was 90.9%. Of the 11 patients, 9 (81.8%) responded to the treatment, 1 with a pathological complete response (pCR) and 8 with a major pathological response (MPR). No adverse events of grade 3 or higher occurred. Neither PD-L1 expression nor TMB was significantly correlated with treatment response. Analysis of TIME revealed that the fraction of CD8 T cell in the invasive margin was higher in responders than non-responders before treatment. TAM2 in the tumor center and CD8 T cell in the invasive margin was significantly increased after combination therapy, which suggested that combination therapy promoted infiltration of CD8 T cells, thereby exerting an antitumor effect.
Immunotherapy plus anti-angiogenic drugs and chemotherapy is a promising treatment strategy for advanced or metastatic GC patients. Tumor infiltration CD8 T cells may serve as potential predictive biomarker.
免疫疗法联合化疗已被证实对晚期或转移性胃癌（GC）有效。抗程序性死亡蛋白1（PD-1）联合抗血管生成药物在晚期胃癌的后续治疗中显示出有前景的活性和可耐受的毒性。本研究的目的是评估抗PD-1联合抗血管生成药物及化疗在晚期或转移性GC中的疗效和安全性，并探索与反应相关的潜在生物标志物。
我们回顾性分析了30例接受PD-1联合抗血管生成药物及化疗的人表皮生长因子受体2（HER2）阴性的晚期或转移性GC患者。当患者在联合治疗后能够接受手术切除时，定义为转化治疗。临床数据从病历中获取。我们使用下一代测序（NGS）对基线基因突变和肿瘤突变负荷（TMB）进行探索性生物标志物分析，通过免疫组织化学（IHC）检测PD-L1，通过多重免疫荧光检测肿瘤免疫微环境（TIME）。
在研究期间，共有30例患者接受了抗PD-1联合抗血管生成药物及化疗。客观缓解率（ORR）为76.7%[95%置信区间（CI）：57.7-90.1%]，疾病控制率（DCR）为86.7%（95%CI：69.3-96.2%）。共有11例患者（36.7%）实现了转化治疗并接受了手术。R0切除率为90.9%。在这11例患者中，9例（81.8%）对治疗有反应，1例达到病理完全缓解（pCR），8例达到主要病理反应（MPR）。未发生3级或更高等级的不良事件。PD-L1表达和TMB均与治疗反应无显著相关性。TIME分析显示，治疗前反应者的肿瘤浸润边缘CD8 T细胞比例高于无反应者。联合治疗后肿瘤中心的TAM2和肿瘤浸润边缘的CD8 T细胞显著增加，这表明联合治疗促进了CD8 T细胞的浸润，从而发挥抗肿瘤作用。
免疫疗法联合抗血管生成药物及化疗是晚期或转移性GC患者一种有前景的治疗策略。肿瘤浸润性CD8 T细胞可能作为潜在的预测生物标志物。
