Noninvasive early identification of durable clinical benefit from immune checkpoint inhibition: a prospective multicenter study (NCT04566432)  

作　　者：Xinghao Ai Bo Jia Zhiyi He Junping Zhang Minglei Zhuo Jun Zhao Zhe Wang Jiexia Zhang Zaiwen Fan Xiaotong Zhang Chong Li Feng Jin Ziming Li Xia Ma Hao Tang Xiang Yan Wei Li Yuanyuan Xiong Huan Yin Rongrong Chen Shun Lu 

机构地区：[1]Shanghai Lung Cancer Center,Shanghai Chest Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [2]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Thoracic Medical Oncology,Peking University Cancer Hospital&Institute,Beijing,China [3]Department of Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Guangxi Medical University,Nanning,China [4]Department of Thoracic Oncology,Cancer Center,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Third Hospital of Shanxi Medical University,Taiyuan,China [5]Department of Thoracic Surgery,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen,China [6]State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,Guangzhou Institute of Respiratory Health,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,China [7]Department of Pulmonary and Critical Care Medicine,Air Force Medical Center,PLA,Beijing,China [8]Department of Pulmonary and Critical Care Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [9]Department of Pulmonary and Critical Care Medicine,Third Affiliated Hospital of Soochow University,First People’s Hospital of Changzhou,Changzhou,China [10]Oncology Department,Qianjiang National Hospital,Chongqing,China [11]Department of Respiratory and Critical Care Medicine,Beijing Youan Hospital,Capital Medical University,Beijing,China [12]Department of Respiratory and Critical Care Medicine,Shanghai Changzheng Hospital,Naval Medical University,Shanghai,China [13]Department of Thoracic Surgery,Peking University People’s hospital,Beijing,China [14]Department of Respiratory and Critical Care Medicine,Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,China [15]GenePlus-Beijin

出　　处：《Signal Transduction and Targeted Therapy》2025年第1期350-359,共10页信号转导与靶向治疗(英文)

基　　金：supported by the National Natural Science Foundation of China(82030045 and 82241227 to S.L.);National Multi-disciplinary Treatment Project for Major Diseases(2020NMDTP to S.L.);Collaborative Innovation Center for Clinical and Translational Science by Ministry of Education&Shanghai(CCTS-202204 and CCTS202304 to S.L.);Shanghai Chest Hospital Basic Research Project(2023YNKT-1 to S.L.);the Natural Science Foundation of Shanghai(22ZR1457500 to X.A.);the National Natural Science Foundation of China(82141117 to M.Z.);the Capital’s Funds for Health Improvement and Research(2022-2-1023 to M.Z.);WU JIEPING MEDICAL FOUNDATION(320.6750.2021-16-19 to M.Z.);Guangzhou Life oasis public service center Research and exchange program in thefield of health(1-35 to M.Z.);Beijing Xisike Clinical Oncology Research Foundation(Y-pierrefabre202101-0099 to M.Z.).

摘　　要：Immune checkpoint inhibitors(ICIs)have changed the treatment landscape for patients with non-small cell lung cancer(NSCLC).In spite of durable responses in some patients,many patients develop early disease progression during the ICI treatment.Thus,early identification of patients with no durable benefit would facilitate the clinical decision for these patients.In this prospective,multicenter study,101 non-EGFR/ALK patients who received ICI treatment were enrolled after screening 328 stage III-IV NSCLC patients.At the date of cutoff,83 patients were eligible for ICI efficacy evaluation,with 56 patients having progress-free survival(PFS)over 6 months,which was defined as durable clinical benefit(DCB).A multimodal model was established by integrating normalized bTMB,early dynamic of ctDNA and thefirst RECIST response.This model could robustly predict DCB with area under the curve(AUC)of 0.878,sensitivity of 79.2%at 86.4%specificity(accuracy=80.0%).This model was further validated in the independent cohort of the DIREct-On study with AUC of 0.887,sensitivity of 94.7%at 85.3%specificity(accuracy=90.3%).Patients with higher predict scores had substantially longer PFS than those with lower scores(training cohort:median PFS 13.6 vs 4.2 months,P<0.001,HR=0.24;validation cohort:median PFS 11.0 vs 2.2 months,P<0.001,HR=0.17).Taken together,these results demonstrate that integrating early changes of ctDNA,normalized bTMB,and thefirst RECIST response can provide accurate,noninvasive,and early prediction of durable benefits for NSCLC patients treated with ICIs.Further prospective studies are warranted to validate thesefindings and guide clinical decision-making for optimal immunotherapy in NSCLC patients.

关 键 词：PROSPECTIVE clinical SPECIFICITY 

分 类 号：R73[医药卫生—肿瘤]