Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01)

被引：125

作者：

Wang, Zhijie ^{[1
]}

Wu, Lin ^{[2
]}

Li, Baolan ^{[3
]}

Cheng, Ying ^{[4
]}

Li, Xiaoling ^{[5
]}

Wang, Xicheng ^{[6
]}

Han, Liang ^{[7
]}

Wu, Xiaohong ^{[8
]}

Fan, Yun ^{[9
]}

Yu, Yan ^{[10
]}

Lv, Dongqing ^{[11
]}

Shi, Jianhua ^{[12
]}

Huang, Jianjin ^{[13
]}

Zhou, Shaozhang ^{[14
]}

Han, Baohui ^{[15
]}

Sun, Guogui ^{[16
]}

Guo, Qisen ^{[17
]}

Ji, Youxin ^{[18
]}

Zhu, Xiaoli ^{[19
]}

Hu, Sheng ^{[20
]}

Zhang, Wei ^{[21
]}

Wang, Qiming ^{[22
]}

Jia, Yuming ^{[23
]}

Wang, Ziping ^{[24
]}

Song, Yong ^{[25
]}

Wu, Jingxun ^{[26
]}

Shi, Meiqi ^{[27
]}

Li, Xingya ^{[28
]}

Han, Zhigang ^{[29
]}

Liu, Yunpeng ^{[30
]}

Yu, Zhuang ^{[31
]}

Liu, An-Wen ^{[32
]}

Wang, Xiuwen ^{[33
]}

Zhou, Caicun ^{[34
]}

Zhong, Diansheng ^{[35
]}

Miao, Liyun ^{[36
]}

Zhang, Zhihong ^{[37
]}

Zhao, Hui ^{[38
]}

Yang, Jun ^{[39
]}

Wang, Dong ^{[40
]}

Wang, Yingyi ^{[41
]}

Li, Qiang ^{[42
]}

Zhang, Xiaodong ^{[43
]}

Ji, Mei ^{[44
]}

Yang, Zhenzhou ^{[45
]}

Cui, Jiuwei ^{[46
]}

Gao, Beili ^{[47
]}

Wang, Buhai ^{[48
]}

Liu, Hu ^{[37
]}

Nie, Lei ^{[49
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, CAMS Key Lab Translat Res Lung Canc, State Key Lab Mol Oncol,Canc Hosp, Dept Med Oncol,Natl Canc Ctr,Natl Clin Res Ctr Ca, Beijing, Peoples R China

[2] Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Xiangya Sch Med, Changsha, Peoples R China

[3] Capital Med Univ, Beijing Chest Hosp, Beijing, Peoples R China

[4] Jilin Canc Hosp, Changchun, Peoples R China

[5] Liaoning Canc Hosp & Inst, Shenyang, Peoples R China

[6] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Sch Clin Med, Guangzhou, Peoples R China

[7] Xuzhou Cent Hosp, Xuzhou, Jiangsu, Peoples R China

[8] Jiangnan Univ, Affiliated Hosp, Wuxi, Jiangsu, Peoples R China

[9] Univ Chinese Acad Sci, Canc Hosp, Hangzhou, Peoples R China

[10] Harbin Med Univ, Canc Hosp, Harbin, Peoples R China

[11] Taizhou Hosp Zhejiang Prov, Linhai, Peoples R China

[12] Linyi Canc Hosp, Linyi, Shandong, Peoples R China

[13] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China

[14] Guangxi Med Univ Affiliated Tumor Hosp, Nanning, Peoples R China

[15] Shanghai Chest Hosp, Shanghai, Peoples R China

[16] Tangshan Peoples Hosp, Tangshan, Peoples R China

[17] Shangdong Canc Hosp, Jinan, Peoples R China

[18] Qingdao Cent Hosp, Qingdao, Peoples R China

[19] Zhongda Hosp Southeast Univ, Nanjing, Peoples R China

[20] Hubei Canc Hosp, Wuhan, Peoples R China

[21] Nanchang Univ, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China

[22] Henan Canc Hosp, Zhengzhou, Peoples R China

[23] Second Peoples Hosp Yibin, Yibin, Peoples R China

[24] Peking Univ Canc Hosp, Beijing, Peoples R China

[25] Nanjing Univ, Jinling Hosp, Sch Med, Nanjing, Peoples R China

[26] Xiamen Univ, Affiliated Hosp 1, Xiamen, Peoples R China

[27] Jiangsu Canc Hosp, Nanjing, Peoples R China

[28] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Peoples R China

[29] Xinjiang Med Univ, Affiliated Tumor Hosp, Urumqi, Peoples R China

[30] China Med Univ, Hosp 1, Shenyang, Peoples R China

[31] Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China

[32] Nanchang Univ, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China

[33] Shandong Univ, Qilu Hosp, Jinan, Peoples R China

[34] Shanghai Pulm Hosp, Shanghai, Peoples R China

[35] Tianjin Med Univ, Gen Hosp, Tianjin, Peoples R China

[36] Nanjing Univ, Med Sch, Affiliated Drum Tower Hosp, Nanjing, Peoples R China

[37] Anhui Prov Canc Hosp, Hefei, Peoples R China

[38] Anhui Med Univ, Hosp 2, Hefei, Peoples R China

[39] Guangzhou Med Univ, Affiliated Hosp 2, Guangzhou, Peoples R China

[40] Daping Hosp, Army Med Ctr PLA, Daping, Peoples R China

[41] Peking Union Med Coll Hosp, Beijing, Peoples R China

[42] Tongji Univ, Shanghai East Hosp, Shanghai, Peoples R China

[43] Nantong Tumor Hosp, Nantong, Peoples R China

[44] First Peoples Hosp Changzhou, Changzhou, Peoples R China

[45] Chongqing Univ, Affiliated Hosp 2, Chongqing, Peoples R China

[46] First Hosp Jilin Univ, Jilin, Jilin, Peoples R China

[47] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai, Peoples R China

[48] Subei Peoples Hosp Jiangsu Prov, Yanghzou, Peoples R China

[49] Shanxi Prov Tumor Hosp, Xian, Peoples R China

[50] Shanxi Prov Peoples Hosp, Taiyuan, Peoples R China

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2023年 / 41卷 / 03期

基金：

北京市自然科学基金;

关键词：

PD-1; EFFICACY; SAFETY; NIVOLUMAB; RECURRENT; ANTIBODY;

D O I：

10.1200/JCO.22.00727

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 METHODSPatients (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.

引用

页码：651 / +

页数：15