目的 探究曲妥珠单抗德卢替康（T-DXd）联合IP方案（伊立替康+顺铂）治疗HER2阳性晚期胃癌的近期疗效、远期预后、安全性及对患者血清肿瘤标志物的影响。 方法 采用前瞻性、随机、对照研究设计，纳入2021年8月至2023年8月期间于滕州市中心人民医院就诊的HER2阳性晚期胃癌患者96例。采用随机数字表法将患者分为观察组（n = 48，曲妥珠单抗德卢替康+ IP方案）与对照组（n = 48，曲妥珠单抗+ IP方案）。观察两组客观缓解率（ORR）、疾病控制率（DCR），统计总生存期（OS）、无进展生存期（PFS）、2年生存率，并评价疗法安全性，同时检测血清肿瘤标志物［糖类抗原724（CA72-4）、糖类抗原199（CA19-9）、癌胚抗原（CEA）、血管内皮生长因子（VEGF）］、血清炎症指标［单核细胞趋化蛋白-1（MCP-1）、白细胞介素-1β（IL-1β）］与免疫应答指标［可溶性程序性死亡配体-1（sPD-L1）、IL-2、γ干扰素（IFN-γ）］。 结果 观察组ORR为58.33%，与对照组（45.83%）比较，差异无统计学意义（P > 0.05）；DCR为87.50%，高于对照组（70.83%）（P < 0.05）。治疗后，两组CEA、CA19-9、CA72-4、VEGF、MCP-1与IL-1β水平均较治疗前下降（P < 0.05），且观察组CEA、CA19-9、CA72-4、VEGF与MCP-1水平均低于对照组（P < 0.05）。观察组≥ 3级中性粒细胞减少及贫血发生率均高于对照组（P < 0.05），心脏毒性发生率差异无统计学意义（P > 0.05）。观察组中位PFS与中位OS均高于对照组（P < 0.05），2年总生存率差异均无统计学意义（P > 0.05）。 结论 T-DXd联合IP方案有助于提高HER2阳性晚期胃癌患者近期疗效，降低血清肿瘤标志物及VEGF、MCP-1水平，并延长中位PFS与OS，虽存在血液学及胃肠道不良事件增加风险，但整体安全性可控，提示该联合方案可能成为该人群新的治疗选择。

Objective To investigate the short-term efficacy， long-term prognosis， and safety of trastuzumab deruxtecan （T-DXd） combined with the IP chemotherapy regimen （irinotecan + cisplatin） in the treatment of HER2-positive advanced gastric cancer， as well as its effects on the serum tumor markers of patients. Methods A prospective， randomized， and controlled study design was employed to enroll 96 patients with HER2-positive advanced gastric cancer who received treatment at the hospital from August 2021 to August 2023. The patients were randomly assigned to the observation group （n = 48， treated with the T-DXd + IP chemotherapy regimen） and the control group （n = 48， treated with the trastuzumab + IP chemotherapy regimen） using the random number table method. The objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and 2-year survival rate were compared between the two groups， and the safety of the treatment was assessed. Serum tumor markers ［carbohydrate antigen 724 （CA72-4）， carbohydrate antigen 199 （CA19-9）， carcinoembryonic antigen （CEA）， vascular endothelial growth factor （VEGF）］， serum inflammatory indicators ［monocyte chemoattractant protein-1 （MCP-1）， interleukin-1β （IL-1β）］， and immune response indicators ［soluble programmed death ligand-1 （sPD-L1）， IL-2， interferon-γ （IFN-γ）］ were measured. Results The objective response rate （ORR） of the observation group was 58.33%， which showed no significant difference compared to that of the control group （45.83%） （P > 0.05）. The disease control rate （DCR） in the observation group was 87.50%， which was higher than the 70.83% in the control group （P < 0.05）. After treatment， the levels of carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， carbohydrate antigen 72-4 （CA72-4）， vascular endothelial growth factor （VEGF）， monocyte chemoattractant protein-1 （MCP-1）， and interleukin-1β （IL-1β） in both groups decreased from the baseline levels （P < 0.05）. Moreover， the above-mentioned levels in the observation group were lower than those in the control group （P < 0.05）. The incidence rates of grade 3 or higher neutropenia and anemia in the observation group were higher than those in the control group （P < 0.05）， while there was no statistical significance in the incidence rate of cardiac toxicity between the two groups （P > 0.05）. The median progression-free survival （PFS） and median overall survival （OS） were significantly higher in the test group than those in the control group （P < 0.05）， and there were no statistical differences in the 2-year overall survival rate （P > 0.05）. Conclusion T-DXd combined with IP chemotherapy regimen improves the short-term efficacy in patients with HER2-positive advanced gastric cancer， reduces the serum levels of tumor markers， VEGF， and MCP-1， and prolongs the median PFS and OS. Although it is associated with an increased risk of hematological and gastrointestinal adverse events， the overall safety is controllable， suggesting that the combined regimen may become a new treatment option for this population.