Ying Zhou, Chenchen Zhu, Zhen Shen, Yanhu Xie, Wei Zhang, Jing Zhu, Tianjiao Zhang, Min Li, Jiwei Qin, Shuai Yin, Rongzhu Chen, Wei Wei, Sinan Sun, Guihong Wang, Zheng Zhou, Hanhui Yao, Dabao Wu and Björn Nashan
Anna Hung, Kyung Min Lee, Yanhong Li, Julie A. Lynch, Pradeep Poonnen, Bradley J. Hintze, Olga V. Efimova, Candice Yong, Brian Seal, Trudy Pendergraft, Michael Kelley and Shelby D. Reed
Qingqing Zhou, Chenchen Zhu, Zhen Shen, Jing Zhu, Tianjiao Zhang, Min Li, Jiwei Qin, Lili Qian, Chuan Chen, Hanyuan Liu, Zhihao Xu, Dabao Wu, Björn Nashan and Ying Zhou
Wei Nie, Jie Qian, Mi-Die Xu, Kai Gu, Fang-Fei Qian, Jun Lu, Xue-Yan Zhang, Hui-Min Wang, Bo Yan, Bo Zhang, Shu-Yuan Wang, Fang Hu, Chang-Hui Li, Hua Zhong and Bao-Hui Han
Background: Biomarkers for chemotherapy efficacy in non–small cell lung cancer (NSCLC) are lacking. This retrospective study assesses the association between blood-based tumor mutational burden (bTMB) and clinical benefit of chemotherapy. Methods: Clinical and targeted next-generation sequencing data from the OAK trial (training set; n=318) and POPLAR trial (validation set; n=106) in the docetaxel arm were analyzed. The cutoff value of bTMB for outcome prediction was determined based on a time-dependent receiver operating characteristic curve in the training set, and propensity score matching (PSM) was conducted. The primary outcome was overall survival (OS). Durable clinical benefit (DCB) was defined as OS lasting >12 months. Interaction between treatment and bTMB was assessed in the combined set. Results: A lower bTMB was observed in patients with DCB compared with no durable benefit, and in those with a partial response and stable disease compared with progressive disease. The optimized cutoff value of bTMB for predicting OS was 7 single-nucleotide variants per megabase. In the training set, a low bTMB was significantly associated with longer OS and progression-free survival (PFS). The prognostic value of bTMB was confirmed in the validation set and PSM set. The interaction between bTMB and treatment was significant for PFS (interaction P=.043) in the combined set. Mutations in KEAP1 were associated with high bTMB and a lack of benefit from chemotherapy. Conclusions: Low bTMB is associated with a survival advantage in patients with NSCLC treated with docetaxel, suggesting the prognostic and predictive potential of bTMB for determining chemotherapy efficacy.