免疫治疗在胃癌围手术期及转化治疗中的探索  

Exploration of immunotherapy in perioperative and conversion therapy for gastric cancer

作　　者：梁寒 Han Liang(Gastric Cancer Center,Tianjin Medical University Cancer Institute&Hospital,National Clincial Research Center for Cancer,Tianjin’s Clinical Research Center for Cancer,Tianjin Key Laboratory of Digestive Cancer,Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院胃癌中心,国家恶性肿瘤临床医学研究中心,天津市恶性肿瘤临床医学研究中心,天津市消化系统肿瘤重点实验室,天津市300060

出　　处：《中国肿瘤临床》2024年第13期658-662,共5页Chinese Journal of Clinical Oncology

摘　　要：胃癌是中国最常见的恶性肿瘤之一,随着药物治疗的进步,胃癌的治疗已经进入免疫时代。标准D2术后辅助免疫治疗需要筛选免疫优势人群。针对高度微卫星不稳定性/错配修复缺陷(microsatellite instability-high/mismatch repair deficiency,MSIH/dMMR)的局部进展期胃癌,双免序贯新辅助治疗可以获得60%的病理完全缓解(pathological complete response,pCR),值得进一步探索。多项局部进展期胃癌的Ⅱ期研究近期结果显示,与单纯化疗比较,免疫联合化疗可以获得更高的pCR,并且与患者CPS评分正相关。针对Her-2阳性的局部进展期胃癌,靶向治疗+免疫治疗+化疗(下文统称为“靶免化”)新辅助治疗可以获得30%以上的pCR,显著优于单纯化疗或化疗+靶向治疗。针对局部进展期胃癌采取免疫联合同步放化疗可以获得40%以上的pCR,是一种值得探索的治疗模式。局部进展期胃癌新辅助免疫治疗+化疗的Ⅲ期临床研究,近期疗效达到预期,其中Keynote585研究的无事件生存(event-free survival,EFS)和总生存(overall survival,OS)未达到预期,而MATTERHONE和DRAGONⅣ研究远期结果正在随访中。CPS≥5是公认的免疫优势人群,而CPS<1的患者很难从免疫治疗中获益。靶免化模式用于Ⅳ期胃癌转化治疗可以获得较高的手术转化率和pCR率,需要高级别循证证据。Gastric cancer is one of the most common malignancies in China.With the recent progress in drug therapy,the treatment of gastric cancer has entered the immune era.The results of the ATTRACTION-5 trial suggest selecting the optimal patient population for adjuvant immunotherapy after standard D2 gastrectomy.For locally advanced gastric cancer with microsatellite instability-high/mismatch repair deficiency(MSI-H/dMMR),sequential neoadjuvant therapy with double check point inhibitor treatment can achieve a pathological complete response(pCR)of 60%,warranting further exploration.Preliminary phaseⅡstudies for perioperative treatmentof locally advanced gastric cancer suggest that immunotherapy combined with chemotherapy can achieve a higher pCR than perioperative chemotherapy alone,and this improvement positively correlates with the combined positive score(CPS).For HER2-positive locally advanced gastric cancer,a pCR of>30%can be achieved using targeted therapy combined with immunochemotherapy,which is significantly better than chemotherapy alone or chemotherapy plus targeted therapy.For locally advanced gastric cancer,immunotherapy combined with concurrent chemoradiotherapy can achieve a pCR of>40%,making it a promising treatment model for further exploration.Although the short-term effects of phaseⅢtrials of neoadjuvant immunochemotherapy for locally advanced gastric cancer met expectations,the KEYNOTE-585 study did not meet the expectations for event-free survival(EFS)and overall survival(OS).The long-term results from the MATTERHONE and DRAGONⅣtrials are pending.CPS≥5 is recognized as a cutoff for benefiting from immunotherapy,whereas patients with CPS<1 are unlikely to benefit.For patients with stageⅣgastric cancer,targeted therapy combined with immunochemotherapy for conversion therapy may result in a higher success rate of radical resection and postoperative pCR;however,a higher level of evidence-based medical evidence is needed.

关 键 词：胃癌 局部进展期 围手术期治疗 转化治疗 免疫治疗 

分 类 号：R735.2[医药卫生—肿瘤]