期刊论文详细信息
Molecular Cancer
On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial
Rui Wang1  Yueyin Pan2  Yi Geng3  Jian Fang4  Donglin Wang5  Caicun Zhou6  Shengxiang Ren6  Tao Jiang6  Yaxi Zhang7  Jiao Zhang7  Gongyan Chen8  Qiming Wang9  Shundong Cang1,10  Junyan Yu1,11  Sheng Hu1,12  Jianhua Chen1,13  Wei Shi1,14  Zeyu Yang1,14  Jianjun Zou1,14  Renhua Guo1,15  Hui Luo1,16  Ying Cheng1,17  Chunyan Xing1,18  Jianhua Shi1,19  Xingxiang Xu2,20  Yanjun Zhang2,21  Wenxiu Yao2,22  Yong Fang2,23  Dongqing Lv2,24  Zhiwu Wang2,25  Wei Zhang2,26  Xingya Li2,27  Peiguo Cao2,28  Yunchao Huang2,29  Yiping Zhang3,30 
[1] Anhui Chest Hospital, Hefei, China;Anhui Provincial Hospital, Hefei, China;Baoji Central Hospital, Baoji, China;Beijing Cancer Hospital, Beijing, China;Chongqing University Cancer Hospital, Chongqing, China;Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, 200433, Shanghai, China;Genecast Biotechnology Co., Ltd., Wuxi City, China;Harbin Medical University Cancer Hospital, Harbin, China;Henan Cancer Hospital, Zhengzhou, China;Henan Provincial People’s Hospital, Zhengzhou, China;Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China;Hubei Cancer Hospital, Wuhan, China;Hunan Cancer Hospital, Changsha, China;Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China;Jiangsu Province Hospital, Nanjing, China;Jiangxi Cancer Hospital, Nanchang, China;Jilin Cancer Hospital, Changchun, China;Jinan Central Hospital, Jinan, China;LinYi Cancer Hospital, Linyi, China;Northern Jiangsu People’s Hospital, Yangzhou, China;Shaanxi Provincial Cancer Hospital, Xi’an, China;Sichuan Provincial Cancer Hospital, Chengdu, China;Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, China;Taizhou Hospital of Zhejiang Province, Taizhou, China;Tangshan People’s Hospital, Tangshan, China;The First Affiliated Hospital of Nanchang University, Nanchang, China;The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;The Third Xiangya Hospital of Central South University, Changsha, China;Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Centre, Kunming, China;Zhejiang Cancer Hospital, Hangzhou, China;
关键词: immunotherapy;    PD-1;    lung squamous cell carcinoma;    blood tumor mutational burden;    biomarker;   
DOI  :  10.1186/s12943-021-01479-4
来源: Springer
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【 摘 要 】

BackgroundCamrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown.MethodsTumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values.ResultsPretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy.ConclusionOn-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC.Trial registrationClinicalTrials.gov identifier: NCT03668496.

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