Clinical definition of secondary resistance to immunotherapy in non‐small cell lung cancer

Author:

Huang Dingzhi1ORCID,Lin Gen2ORCID,Chu Qian3,Hu Yi4ORCID,Wang Jun5ORCID,Wang Zhijie6,Yang Fan7,Zhong Wenzhao8ORCID,Zhou Chengzhi9ORCID,Zhu Bo10,Ai Xinghao11,Cao Baoshan12,Cao Yabing13,Chen Mingqiu14,Chen Xiaohui15,Chu Tianqing16,Duan Jianchun6ORCID,Fan Yun17,Fang Yong18,Feng Shuitu19,Feng Weineng20,Guo Hui21,Han Chengbo22ORCID,He Yong23ORCID,Hong Shaodong24,Hu Jie25,Huang Meijuan26ORCID,Huang Yan24,Jiang Da27,Jiang Kan2,Jiang Richeng1,Jin Bo28,Jin Shi29ORCID,Li Jisheng30ORCID,Li Min31,Li Ziming11,Li Chao32,Lin Jie33,Liu Anwen34,Liu Si‐Yang Maggie35,Liu Yutao6,Liu Zhefeng4,Liu Zhe36,Liu Zhenhua37,Liu Zhentian38,Liu Zhigang39,Lu Yuping40,Lv Tangfeng41ORCID,Ma Zhiyong42,Miao Qian2,Peng Min43ORCID,Pu Xingxiang44,Ren Xiu Bao45,Shan Jianzhen46,Shan Jinlu47,Shen Peng48,Shen Bo49ORCID,Shi Meiqi49ORCID,Song Yong41ORCID,Song Zhengbo50,Su ChunXia51,Sun Jianguo10,Tian Panwen52ORCID,Wang Jinliang4,Wang Feng15,Wang Huijuan42,Wang Jialei53,Wang Qian54,Wang Wenxian17ORCID,Wang Yan6ORCID,Wu Lin44,Wu Fang55ORCID,Xia Yang56ORCID,Xie Congying57ORCID,Xie Conghua58ORCID,Xin Tao59,Xiong Jianping60,Xu Haipeng2,Xu Song61ORCID,Xu Yiquan2,Xu Bin43,Xu Chunwei41ORCID,Yan Xiaolong62,Yang Zhenzhou63,Yao Wenxiu64,Yu Yao21,Feng Ye65,Yu Zongyang66,Yu Yongfeng11,Yue Dongsheng67,Zhang Haibo68,Zhang HongMei69,Zhang Li3,Zhang Longfeng2,Zhang Qiuyu70,Zhang Tongmei36ORCID,Zhang Bicheng43,Zhao Jun71ORCID,Zhao Mingfang28,Zheng Xiaobin2,Zhong Fengqiao2,Zhou Jin64,Zhou Penghui24,Zhu Zhengfei72,Zou Juntao73,Zou Zihua2ORCID

Affiliation:

1. Department of Thoracic Oncology Tianjin Medical University Cancer Institute and Hospital Tianjin People's Republic of China

2. Department of Thoracic Oncology Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital Fuzhou People's Republic of China

3. Department of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of China

4. Senior Department of Oncology Chinese PLA General Hospital Beijing People's Republic of China

5. Department of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Ji'nan People's Republic of China

6. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing People's Republic of China

7. Department of Thoracic Surgery Peking University People Hospital Beijing People's Republic of China

8. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou People's Republic of China

9. Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases The First Affiliated Hospital of Guangzhou Medical University Guangzhou People's Republic of China

10. Institute of Cancer, Xinqiao Hospital Army Medical University Chongqing People's Republic of China

11. Shanghai Lung Cancer Center, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of China

12. Cancer center Peking University Third Hospital/ Department of medical oncology and radiation sickness, Peking University Third Hospital Beijing People's Republic of China

13. Department of oncology Kiang Wu Hospital Macau People's Republic of China

14. Department of Thoracic Radiation Oncology, Clinical Oncology School of Fujian Medical University Fujian Cancer Hospital Fuzhou People's Republic of China

15. Department of Thoracic Surgery, Clinical Oncology School of Fujian Medical University Fujian Cancer Hospital Fuzhou People's Republic of China

16. Respiratory Department, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of China

17. Department of Medical Oncology Zhejiang Cancer Hospital Hangzhou People's Republic of China

18. Department of Medical Oncology, Sir Run Run Shaw Hospital Zhenjiang University School of Medicine Hangzhou People's Republic of China

19. Department of Medical Oncology Fudan University Shanghai Cancer Center Xiamen Hospital Xiamen People's Republic of China

20. Department of Pulmonary Oncology The First People's Hospital of Foshan Foshan People's Republic of China

21. Department of Medical Oncology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an People's Republic of China

22. Department of Oncology Shengjing Hospital of China Medical University Shenyang People's Republic of China

23. Department of Respiratory Medicine, Xinqiao Hospital Army Medical University Chongqing People's Republic of China

24. State Key Laboratory of Oncology in Southern China Sun Yat‐sen University Cancer Center Guangzhou People's Republic of China

25. Zhongshan Hospital, Fudan University Shanghai Geriatric Center Shanghai People's Republic of China

26. Division of Thoracic Tumor Multimodality Treatment and Department of Medical Oncology, Cancer Center, West China Hospital Sichuan University Chengdu People's Republic of China

27. Department of Oncology The Fourth Affiliated Hospital of Hebei Medical University Shijiazhuang People's Republic of China

28. Department of Medical Oncology The First affiliated hospital of China Medical University Shenyang People's Republic of China

29. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital &Shenzhen Hospital Chinese Academy of Medical Sciences and Perking Union Medical College Shenzhen People's Republic of China

30. Department of Medical Oncology Qilu Hospital of Shandong University Ji'nan People's Republic of China

31. Department of Respiratory Medicine, Xiangya Hospital Central South University Changsha People's Republic of China

32. Department of Pathology Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital Fuzhou People's Republic of China

33. Department of Medical Oncology The Second Affiliated Hospital of Kunming Medical University Kunming People's Republic of China

34. Department of Medical Oncology The Second Affiliated Hospital of Nanchang University Nanchang People's Republic of China

35. Department of Hematology, First Affiliated Hospital Ji'nan University Guangzhou People's Republic of China

36. Department of Medical Oncology, Beijing Chest Hospital Capital Medical University Beijing People's Republic of China

37. Department of Oncology, Shengli Clinical Medical College of Fujian Medical University Fujian Provincial Hospital Fuzhou People's Republic of China

38. Department of Thoracic Oncology,Jiangxi Cancer Hospital Nanchang People's Republic of China

39. Cancer Center The 10th Affiliated Hospital of Southern Medical University Dongguan People's Republic of China

40. Department of Abdominal Oncology Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital Fuzhou People's Republic of China

41. Department of Respiratory Medicine, Affiliated Jinling Hospital Medical School of Nanjing University Nanjing People's Republic of China

42. Department of Respiratory Medicine Henan Cancer Hospital /Affiliated Cancer Hospital of Zhengzhou University Zhengzhou People's Republic of China

43. Cancer center Renmin Hospital of Wuhan University Wuhan People's Republic of China

44. Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha People's Republic of China

45. Department of Biotherapy Tianjin Medical University Cancer Institute and Hospital Tianjin People's Republic of China

46. Department of Medical Oncology The First Affiliated Hospital of Zhejiang University Zhejiang People's Republic of China

47. Department of Medical Oncology, Daping Hospital Army Medical University Chongqing People's Republic of China

48. Department of Oncology, Nanfang Hospital Southern Medical University Guangzhou People's Republic of China

49. Department of Medical Oncology Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Affiliated Cancer Hospital of Nanjing Medical University Nanjing People's Republic of China

50. Department of Clinical Trial Zhejiang Cancer Hospital Hangzhou People's Republic of China

51. Department of Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute Tongji University School of Medicine Shanghai People's Republic of China

52. Department of Pulmonary and Critical Care Medicine, Lung Cancer Center, West China Hospital Sichuan University, Precision Medicine Key Laboratory of Sichuan Province Chengdu People's Republic of China

53. Department of Thoracic Medical Oncology Fudan University Shanghai Cancer Center Shanghai People's Republic of China

54. Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese Medicine Nanjing People's Republic of China

55. Department of Oncology, The Second Xiangya Hospital Central South University Changsha People's Republic of China

56. Department of Respiratory and Critical Care Medicine Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou People's Republic of China

57. Department of Radiation and Medical Oncology Second Affiliated Hospital of Wenzhou Medical University Wenzhou People's Republic of China

58. Department of Pulmonary Oncology Zhongnan Hospital of Wuhan University Wuhan People's Republic of China

59. Department of Oncology The Second Affiliated Hospital of Harbin Medical University Harbin People's Republic of China

60. Department of Oncology The First Affiliated Hospital of Nanchang University Nanchang People's Republic of China

61. Department of Lung Cancer Surgery Tianjin Medical University General Hospital Tianjin People's Republic of China

62. Department of Thoracic Surgery, Tangdu Hospital Air Force Medical University Xi'an People's Republic of China

63. Department of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing People's Republic of China

64. Department of Medical Oncology, Sichuan Cancer Hospital University of Electronic Science and Technology of China Chengdu People's Republic of China

65. Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University Xiamen People's Republic of China

66. Department of Respiratory Medicine, The 900th Hospital of the Joint Logistic Support Force People's Liberation Army of China Fuzhou People's Republic of China

67. Department of Lung Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin People's Republic of China

68. Department of Oncology Guangdong Provincial Hospital of Chinese Medicine Guangzhou People's Republic of China

69. Department of Clinical Oncology, Xijing Hospital Air Force Medical University Xi'an People's Republic of China

70. Institute of Immunotherapy Fujian Medical University Fuzhou People's Republic of China

71. Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing), Department I of Thoracic Oncology Peking University Cancer Hospital and Institute Beijing People's Republic of China

72. Department of Radiation Oncology Fudan University Shanghai Cancer Center Shanghai People's Republic of China

73. Department of Respiratory Medicine The First Affiliated Hospital of Nanchang University Nanchang People's Republic of China

Abstract

AbstractImmune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Publisher

Wiley

Subject

Pulmonary and Respiratory Medicine,Oncology,General Medicine

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