| Title | Allele Frequency-Adjusted Blood-Based Tumor Mutational Burden as a Predictor of Overall Survival for Patients With NSCLC Treated With PD-(L)1 Inhibitors |
| Authors | Wang, Zhijie Duan, Jianchun Wang, Guoqiang Zhao, Jing Xu, Jiachen Han, Jiefei Zhao, Zhengyi Zhao, Jun Zhu, Bo Zhuo, Minglei Sun, Jianguo Bai, Hua Wan, Rui Wang, Xin Fei, Kailun Wang, Shuhang Zhao, Xiaochen Zhang, Yuzi Huang, Mengli Huang, Depei Qi, Chuang Gao, Chan Bai, Yuezong Dong, Hua Xiong, Lei Tian, Yanhua Wang, Di Xu, Chunwei Wang, Wenxian Li, Junling Hu, Xingsheng Cai, Shangli Wang, Jie |
| Affiliation | Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Dept Med Oncol, Natl Canc Ctr,Nat Clin Res Ctr Canc,Canc Hosp, 17 Pan Jia Yuan South Lane, Beijing 100021, Peoples R China 3D Med Inc, Dept Med, Shanghai, Peoples R China Peking Univ, Dept Thorac Med Oncol, Sch Oncol, Beijing Canc Hosp & Inst, Beijing, Peoples R China Army Med Univ, Canc Inst, Xinqiao Hosp, Chongqing, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, GCP Ctr, Natl Canc Ctr, Canc Hosp, Beijing, Peoples R China 3D Med Inc, Bioinformat Dept, Shanghai, Peoples R China Fujian Med Univ, Dept Pathol, Fujian Canc Hosp, Fuzhou, Fujian, Peoples R China Zhejiang Canc Hosp, Dept Chemotherapy, Hangzhou, Zhejiang, Peoples R China |
| Keywords | OPEN-LABEL ATEZOLIZUMAB MULTICENTER DOCETAXEL |
| Issue Date | Apr-2020 |
| Publisher | JOURNAL OF THORACIC ONCOLOGY |
| Abstract | Introduction: Blood-based tumor mutational burden (bTMB) has been studied to identify patients with NSCLC who would benefit from anti-programmed cell death protein 1 (anti-PD-1) or anti-programmed death ligand 1 (anti-PD-L1) therapies. However, it failed to predict overall survival (OS) benefits, which warrants further exploration. Methods: Three independent cohorts of patients with NSCLC treated with immunotherapy were used in this study. A new bTMB algorithm was first developed in the two independent cohorts (POPLAR, N = 211, and OAK, N = 462) and further validated in the third National Cancer Center (NCC) cohort (N = 64). Results: bTMB-H (bTMB >= cutoff point) was not associated with favorable OS after immunotherapy regardless of the cutoff points in either the POPLAR and OAK or the NCC cohorts (p > 0.05) owing to its correlation with the amount of circulating tumor DNA, which was associated with poor OS. In the POPLAR and OAK cohorts, with allele frequency (AF) adjustment, a high AF bTMB (HAF-bTMB, mutation counts with an AF > 5%) was strongly correlated with the amount of circulating tumor DNA (Pearson r = 0.65), whereas a low AF bTMB (LAF-bTMB, mutation counts with an AF <= 5%) was not (Pearson r = 0.09). LAF-bTMB-H was associated with favorable OS (hazard ratio [HR] = 0.70, 95% confidence interval [CI]: 0.52-0.95, p = 0.02), progression-free survival (PFS; HR = 0.62, 95% CI: 0.47-0.80, p < 0.001), and objective response rate (ORR) (p < 0.001) after immunotherapy but not chemotherapy, with a cutoff point of 12 trained in the POPLAR cohort and validated in the OAK cohort. The LAF-bTMB algorithm was further validated in the NCC cohort in which LAF-bTMB-H was associated with OS (HR = 0.20, 95% CI: 0.05-0.84, p = 0.02), PFS (HR = 0.30, 95% CI: 0.13-0.70, p = 0.003), and ORR (p = 0.001). Conclusions: We developed and validated a new LAF-bTMB algorithm as a feasible predictor of OS, PFS, and ORR after anti-PD-(L)1 therapies in patients with NSCLC, which needs to be prospectively validated. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/587522 |
| ISSN | 1556-0864 |
| DOI | 10.1016/j.jtho.2019.12.001 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 |
