1. Toripalimab plus chemotherapy for first line treatment of advanced non-small cell lung cancer (CHOICE-01): final OS and biomarker exploration of a randomized, double-blind, phase 3 trial
- Author
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Jia Zhong, Kailun Fei, Lin Wu, Baolan Li, Zhijie Wang, Ying Cheng, Xiaoling Li, Xicheng Wang, Liang Han, Xiaohong Wu, Yun Fan, Yan Yu, Dongqing Lv, Jianhua Shi, Jianjin Huang, Shaozhang Zhou, Baohui Han, Guogui Sun, Qisen Guo, Youxin Ji, Xiaoli Zhu, Sheng Hu, Wei Zhang, Qiming Wang, Yuming Jia, Ziping Wang, Yong Song, Jingxun Wu, Meiqi Shi, Xingya Li, Zhigang Han, Yunpeng Liu, Zhuang Yu, An-Wen Liu, Xiuwen Wang, Caicun Zhou, Diansheng Zhong, Liyun Miao, Zhihong Zhang, Hui Zhao, Jun Yang, Dong Wang, Yingyi Wang, Qiang Li, Xiaodong Zhang, Mei Ji, Zhenzhou Yang, Jiuwei Cui, Beili Gao, Buhai Wang, Hu Liu, Lei Nie, Mei He, Shi Jin, Wei Gu, Yongqian Shu, Tong Zhou, Jian Feng, Xinmei Yang, Cheng Huang, Bo Zhu, Yu Yao, Sheng Yao, Jianjun Yu, Shang li Cai, Yiran Cai, Jiachen Xu, Wei Zhuang, Xianmin Luo, Jianchun Duan, and Jie Wang
- Subjects
Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57–0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring.
- Published
- 2024
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