Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01). Issue 3 (7th October 2022)

• Record Type: Journal Article
• Authors: Wang, Zhijie; Wu, Lin; Li, Baolan; Cheng, Ying; Li, Xiaoling; Wang, Xicheng; Han, Liang; Wu, Xiaohong; Fan, Yun; Yu, Yan; Lv, Dongqing; Shi, Jianhua; Huang, Jianjin; Zhou, Shaozhang; Han, Baohui; Sun, Guogui; Guo, Qisen; Ji, Youxin; Zhu, Xiaoli; Hu, Sheng; Zhang, Wei; Wang, Qiming; Jia, Yuming; Wang, Ziping; Song, Yong; Wu, Jingxun; Shi, Meiqi; Li, Xingya; Han, Zhigang; Liu, Yunpeng; Yu, Zhuang; Liu, An-Wen; Wang, Xiuwen; Zhou, Caicun; Zhong, Diansheng; Miao, Liyun; Zhang, Zhihong; Zhao, Hui; Yang, Jun; Wang, Dong; Wang, Yingyi; Li, Qiang; Zhang, Xiaodong; Ji, Mei; Yang, Zhenzhou; Cui, Jiuwei; Gao, Beili; Wang, Buhai; Liu, Hu; Nie, Lei; He, Mei; Jin, Shi; Gu, Wei; Shu, Yongqian; Zhou, Tong; Feng, Jian; Yang, Xinmei; Huang, Cheng; Zhu, Bo; Yao, Yu; Tang, Xiongwen; Yu, Jianjun; Maher, Ellen; Feng, Hui; Yao, Sheng; Keegan, Patricia; Wang, Jie;
• Is Part Of: Journal of clinical oncology. Volume 41:Issue 3(2023)
• Page Start: 651
• Page End: 663
• Publication Date: 2022-10-07
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.22.00727
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS: At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION: Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.