Perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy for resectable non-small-cell lung cancer:a multicentre,open-label,single-arm,phase 2 trial(TD-NeoFOUR trial)  

作　　者：Hongtao Duan Changjian Shao Zhilin Luo Tianhu Wang Liping Tong Honggang Liu Xin Yao Jie Lei Jinbo Zhao Yuan Gao Tao Jiang Xiaolong Yan 

机构地区：[1]Department of Thoracic Surgery,Tangdu Hospital,Air Force Medical University,No.1,Xinsi Road,Xi’an,Shaanxi,China [2]Department of Thoracic Surgery,Third Affiliated Hospital,Chongqing Medical University,Chongqing,China [3]State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Biotechnology Center,School of Pharmacy,Air Force Medical University,No.169,Changle West Road,Xi’an,Shaanxi,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第11期5310-5318,共9页信号转导与靶向治疗（英文）

基　　金：funded by the National Natural Science Foundation of China(Grant No.82173252);the Miaozi Talent Fund of Tangdu Hospital,Air Force Medical University.

摘　　要：This open-label,single-arm,phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab combined with anlotinib and chemotherapy,followed by adjuvant sintilimab,for resectable NSCLC.Forty-five patients received anlotinib(10 mg,QD,PO,days 1-14),sintilimab(200 mg,day 1),and platinum-based chemotherapy of each three-week cycle for 3 cycles,followed by surgery within 4-6 weeks.Adjuvant sintilimab(200 mg)was administered every 3 weeks.The primary endpoint was achieving a pathological complete response(pCR).From June 10,2021 through October 10,2023,45 patients were enrolled and composed the intention-to-treat population.Twenty-six patients(57.8%)achieved pCR,and 30(66.7%)achieved major pathological response(MPR).Forty-one patients underwent surgery.In the per-protocol set(PP set),63.4%(26/41)achieved pCR,and 73.2%achieved MPR.The median event-free survival was not attained(95%CI,25.1-NE).During the neoadjuvant treatment phase,grade 3 or 4 treatment-related adverse events were observed in 25 patients(55.6%),while immune-related adverse events were reported in 7 patients(15.6%).We assessed vascular normalization and infiltration of immune-related cells by detecting the expression of relevant cell markers in NSCLC tissues with mIHC.Significant tumor microenvironment changes were observed in pCR patients,including reduced VEGF+cells and CD4+Foxp3+Treg cells,and increased perivascular CD4+T cells,CD39+CD8+T cells,and M1 macrophages.In conclusion,perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment(ClinicalTrials.gov NCT05400070).

关 键 词：CHEMOTHERAPY NEOADJUVANT PHASE 

分 类 号：R734.2[医药卫生—肿瘤]