中国普通外科杂志2025，Vol.34Issue(10)：2106-2118,13.DOI:10.7659/j.issn.1005-6947.250489
基于真实世界的微卫星稳定型晚期结直肠癌免疫联合策略优化研究
Optimization of immunotherapy combination strategies for microsatellite-stable advanced colorectal cancer:a real-world study
摘要
Abstract
Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy. Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration. Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007). Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.关键词
结直肠肿瘤/微卫星稳定/免疫疗法/贝伐珠单抗/抗肿瘤联合化疗方案Key words
Colorectal Neoplasms/Microsatellite Stability/Immunotherapy/Bevacizumab/Antineoplastic Combined Chemo-therapy Protocols分类
医药卫生引用本文复制引用
苟悦,曾珊,胡尔雅,刘萍,曾梦思,骆晴晴,张向阳,蔡长景,申竑,赵枫..基于真实世界的微卫星稳定型晚期结直肠癌免疫联合策略优化研究[J].中国普通外科杂志,2025,34(10):2106-2118,13.基金项目
国家自然科学基金资助项目(82373275,82403920) （82373275,82403920）
湖南自然科学基金资助项目(2024JJ6662). （2024JJ6662）
