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

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.

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Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2024-12-24
DOI
https://doi.org/10.1038/s41392-024-02087-6
Citations
10
Primary Topic
Cancer Genomics and Diagnostics
Type
article
Field-Weighted Citation Impact
2.85

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article

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

Xianmin Luo, Shaozhang Zhou, Yunpeng Liu, Y. Wang et al.
10 citations
Signal Transduction and Targeted Therapy
Cancer Genomics and Diagnostics
2.85
article

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

Xianmin Luo, Shaozhang Zhou, Yunpeng Liu, Y. Wang, Shang li Cai, Shi Jin, Hui Zhao, Youxin Ji, Yao Yu, Tong Zhou, Buhai Wang, Baohui Han, Yongqian Shu, Meiqi Shi, Jiuwei Cui, Beili Gao, Liyun Miao, Xiaohong Wu, Bo Zhu, Wei Gu, Dongqing Lv, Yiran Cai, Kailun Fei, Jianchun Duan, Jian Feng, Guogui Sun, Xiaoli Zhu, Qisen Guo, Lin Wu, Mei He, Xiaoling Li, Xiaodong Zhang, Hu Liu, Dong Wang, Zhijie Wang, Zhihong Zhang, Qiang Li, Jie Wang, Wei Zhang, Zhigang Han, Yong Song, Lei Nie, Yan Yu, Wei Zhuang, Yun Fan, Xin‐Mei Yang, Jianhua Shi, Yu Zhuang, Sheng Yao, Caicun Zhou, Jiachen Xu, Diansheng Zhong, Xiuwen Wang, Ying Cheng, Jia Zhong, Mei Ji, Zhenzhou Yang, Baolan Li, Jun Yang, Ziping Wang, Anwen Liu, Xicheng Wang, Liang Han, XingYa Li, Sheng Hu, Yuming Jia, Jingxun Wu, Jianjun Yu, Jianjin Huang, Cheng Huang, Qiming Wang
article en
10 citations

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.

Signal Transduction and Targeted TherapyVol. 9(1)
Qingdao University (CN), Central South University (CN), Nanchang University (CN), Army Medical University (CN), Xinjiang Medical University (CN), Harbin Medical University (CN), Chongqing University (CN), Shanxi Medical University (CN), Capital Medical University (CN), Guangdong Pharmaceutical University (CN), Dalian Medical University (CN), Jilin University (CN), Anhui Medical University (CN), Nantong University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Wenzhou Medical University (CN), Nanjing General Hospital of Nanjing Military Command (CN), Peking Union Medical College Hospital (CN), Ruijin Hospital (CN), Tianjin Medical University General Hospital (CN), Shanghai Chest Hospital (CN), Affiliated Hospital of Nantong University (CN), First Affiliated Hospital of Xiamen University (CN), National Cancer Center (US), Second Affiliated Hospital of Guangzhou Medical University (CN), Daping Hospital (CN), Peking University Cancer Hospital (CN), Second Affiliated Hospital of Chongqing Medical University (CN), Tangshan People's Hospital (CN), Jilin Province Tumor Hospital (CN), BioReliance (United States) (US), Tumor Hospital of Xinjiang Medical University (CN), Shanxi Provincial Cancer Hospital (CN), Burning Rock Biotech (China) (CN), Third Affiliated Hospital of Harbin Medical University (CN), Nantong Tumor Hospital (CN), The First People's Hospital of Changzhou (CN), Zhongda Hospital Southeast University (CN), Beijing Chest Hospital (CN), Second Affiliated Hospital of Nanchang University (CN), Nanjing Drum Tower Hospital (CN), Wuxi Fourth People's Hospital (CN), Hunan Cancer Hospital (CN), Affiliated Hospital of Qingdao University (CN), Xinqiao Hospital (CN), Qingdao Municipal Hospital (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), First Hospital of Jilin University (CN), Shanghai Pulmonary Hospital (CN), Shanghai East Hospital (CN), Jiangsu Cancer Hospital (CN), Anhui Provincial Hospital (CN), Xuzhou Central Hospital (CN), First Hospital of Jiaxing (CN), First Hospital of China Medical University (CN), Cancer Hospital of Chinese Academy of Medical Sciences (CN), Henan Cancer Hospital (CN), Fujian Provincial Cancer Hospital (CN), Second Affiliated Hospital of Anhui Medical University (CN), Jiangsu Province Hospital (CN), Tumor Hospital of Guangxi Medical University (CN), First Affiliated Hospital of Zhengzhou University (CN), Second People’s Hospital of Yibin (CN), Second Affiliated Hospital of Zhejiang University (CN), Zhejiang Taizhou Hospital (CN), Shanxi Provincial People’s Hospital (CN), Hubei Cancer Hospital (CN), Liaoning Cancer Hospital & Institute (CN), Qilu Hospital of Shandong University (CN), First Affiliated Hospital of Nanchang University (CN), University of Chinese Academy of Sciences (CN), Hangzhou Cancer Hospital (CN), Nanjing Medical University (CN), Chongqing Medical University (CN), Nanjing University (CN), China Medical University (CN), Guangzhou Medical University (CN)
Shanghai Junshi Biosciences, National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 8%
Cancer Genomics and Diagnostics
2.85
DOIOpen Access PDFOpenAlex
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