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

Author:

Wang Zhijie1,Wu Lin2ORCID,Li Baolan3,Cheng Ying4ORCID,Li Xiaoling5,Wang Xicheng6,Han Liang7,Wu Xiaohong8,Fan Yun9,Yu Yan10,Lv Dongqing11,Shi Jianhua12,Huang Jianjin13,Zhou Shaozhang14,Han Baohui15,Sun Guogui16,Guo Qisen17,Ji Youxin18,Zhu Xiaoli19,Hu Sheng20,Zhang Wei21,Wang Qiming22ORCID,Jia Yuming23,Wang Ziping24,Song Yong25,Wu Jingxun26,Shi Meiqi27,Li Xingya28,Han Zhigang29,Liu Yunpeng30,Yu Zhuang31ORCID,Liu An-Wen32,Wang Xiuwen33,Zhou Caicun34,Zhong Diansheng35,Miao Liyun36ORCID,Zhang Zhihong37,Zhao Hui38,Yang Jun39,Wang Dong40,Wang Yingyi41,Li Qiang42,Zhang Xiaodong43,Ji Mei44,Yang Zhenzhou45,Cui Jiuwei46,Gao Beili47,Wang Buhai48,Liu Hu37ORCID,Nie Lei49,He Mei50ORCID,Jin Shi51,Gu Wei52ORCID,Shu Yongqian53,Zhou Tong54,Feng Jian55,Yang Xinmei56,Huang Cheng57,Zhu Bo58,Yao Yu59,Tang Xiongwen6061ORCID,Yu Jianjun60,Maher Ellen60,Feng Hui6061,Yao Sheng6061ORCID,Keegan Patricia60ORCID,Wang Jie1ORCID

Affiliation:

1. CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

2. Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China

3. Beijing Chest Hospital, Capital Medical University, Beijing, China

4. Jilin Cancer Hospital, Changchun, China

5. Liaoning Cancer Hospital & Institute, Shenyang, China

6. The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China

7. Xuzhou Central Hospital, Xuzhou, China

8. Jiangnan University Affiliated Hospital, Wuxi, China

9. Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China

10. Harbin Medical University Cancer Hospital, Harbin, China

11. Taizhou Hospital of Zhejiang Province, Linhai, China

12. Linyi Cancer Hospital, Linyi, China

13. The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

14. Guangxi Medical University Affiliated Tumor Hospital, Nanning, China

15. Shanghai Chest Hospital, Shanghai, China

16. Tangshan People's Hospital, Tangshan, China

17. Shangdong Cancer Hospital, Jinan, China

18. Qingdao Central Hospital, Qingdao, China

19. Zhongda Hospital Southeast University, Nanjing, China

20. Hubei Cancer Hospital, Wuhan, China,

21. The First Affiliated Hospital of Nanchang University, Nanchang, China

22. Henan Cancer Hospital, Zhengzhou, China

23. The Second People's Hospital of Yibin, Yibin, China

24. Peking University Cancer Hospital, Beijing, China

25. Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

26. The First Affiliated Hospital of Xiamen University, Xiamen, China

27. Jiangsu Cancer Hospital, Nanjing, China

28. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

29. Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China

30. The First Hospital of China Medical University, Shenyang, China

31. The Affiliated Hospital of Qingdao University, Qingdao, China

32. The Second Affiliated Hospital of Nanchang University, Nanchang, China

33. Qilu Hospital of Shandong University, Jinan, China

34. Shanghai Pulmonary Hospital, Shanghai, China

35. Tianjin Medical University General Hospital, Tianjin, China

36. Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China

37. Anhui Provincial Cancer Hospital, Hefei, China

38. The Second Hospital of Anhui Medical University, Hefei, China

39. The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

40. Army Medical Center of PLA, Daping Hospital, Daping, China

41. Peking Union Medical College Hospital, Beijing, China

42. Shanghai East Hospital of Tongji University, Shanghai, China

43. Nantong Tumor Hospital, Nantong, China

44. The First People's Hospital of Changzhou, Changzhou, China

45. The Second Affiliated Hospital of Chongqing University, Chongqing, China

46. The First Hospital of Jilin University, Jilin, China

47. Ruijin Hospital Shanghai Jiaotong University, School of Medicine, Shanghai, China

48. Subei People's Hospital of Jiangsu Province, Yanghzou, China

49. Shanxi Provincial Tumor Hospital, Xian, China

50. Shanxi Provincial People's Hospital, Taiyuan, China

51. Cancer Hospital of Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China

52. Nanjing First Hospital, Nanjing, China

53. The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

54. ChangZhou Cancer Hospital, Changzhou, China

55. Affiliated Hospital of Nantong University, Nantong, China

56. Jiaxing No. 1 Hospital, Jiaxing, China

57. Fujian Cancer Hospital, Fuzhou, China

58. Xinqiao Hospital of Army Medical University, Chongqing, China

59. First Affiliated Hospital of Xi'an Jiaotong University, Xian, China

60. TopAlliance Biosciences, Rockville, MD

61. Shanghai Junshi Biosciences, Shanghai, China

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3