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The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.


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Uncommon/rare oncogenic drivers in non‐small cell lung cancer: Consensus and contention

Show Author's information Yi‐Long Wu1( )Shun Lu2Ying Cheng3Qing Zhou1 ( )Hai‐Yan Tu1( )Qing‐Hua Zhou4Lv‐Hua Wang5Li Zhang6Jian‐Ying Zhou7Cheng Huang8Ming Chen6Cheng‐Ping Hu9Shao‐Kun Chuai10Xiao‐Nan Wang11Xiao‐Qing Liu12Ji‐Wei Liu13Peng‐Hui Zhou6Wei‐Zhi Chen14Ling‐Hua Yan15Yun‐Peng Liu16An‐Wen Liu17Xu‐Chao Zhang1Hui Li3Rong‐Rong Chen18Dong‐Mei Lin19Cong‐Ying Xie20Zheng‐Fei Zhu21Hui‐Ying Liang1Yong Song22Xiao‐Rong Dong23Ming‐Fang Zhao16Gui‐Bin Qiao1Jiu‐Wei Cui24Zi‐Ming Li2Zhi‐Jie Wang25Xiao‐Yuan Chen26Nong Yang27Gen Lin8Pan‐Wen Tian4Yun Fan28Qi‐Bin Song29Yuan Chen30Jian‐Chun Duan25Jia‐Lei Wang21Bo Zhu31Bu‐Hai Wang32Jun Zhao19Qi‐Tao Yu33Li‐Feng Wang34Hai‐Bo Zhang35Jie Hu36Rui Ma37Tong‐Mei Zhang38Jie Lin39Qian Chu30Sheng‐Xiang Ren40Yu Yao41Lin Wu27Hui‐Juan Wang42Fang Wu43Wen‐Zhao Zhong1Yi Hu12Ke‐Neng Chen19Jian Zhao44Li Zhang45Fan Yang46Qun Wang36Dong‐Sheng Yue47Jian‐Ya Zhou7Peng Shen48Jia‐Tao Zhang1Xiao‐Long Yan49Mei‐Juan Huang4Wei‐Neng Feng50Li Li51 Chinese Association of Lung Cancer, Guangdong Association of Clinical Trials (GACT)/Chinese Thoracic Oncology Group (CTONG)
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
Jilin Cancer Hospital, Changchun, China
West China Hospital, Sichuan University, Chengdu, China
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China
Sun Yat‐sen University Cancer Center, Guangzhou, China
The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
FuJian Cancer Hospital, Fuzhou, China
Xiangya Hospital of Central South University, Changsha, China
Burning Rock Biotech Co., Ltd., Guangzhou, China
Nanjing Geneseeq Technology Inc., Nanjing, China
Chinese PLA General Hospital, Beijing, China
The First Affiliated Hospital of Dalian Medical University, Dalian, China
Wuxi Genecast Biotechnology Co., Ltd., Wuxi, China
Shanghai Tongshu Biotechnology Co., Ltd., Shanghai, China
The First Hospital of China Medical University, Shenyang, China
The Second Affiliated Hospital of Nanchang University, Nanchang, China
Beijing GenePlus Technology Co., Ltd., Beijing, China
Beijing Cancer Hospital, Beijing, China
The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Fudan University Shanghai Cancer Center, Shanghai, China
General Hospital of Eastern Theater Command, Nanjing, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
The First Bethune Hospital of Jilin University, Changchun, China
Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
School of Medicine, Tsinghua University, Beijing, China
Hunan Cancer Hospital, Changsha, China
Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China
Xinqiao Hospital, Army Medical University, Chongqing, China
Subei People's Hospital Affiliated to Nanjing Medical University, Yangzhou, China
Guangxi Medical University Cancer Hospital, Nanning, China
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
Zhongshan Hospital, Fudan University, Shanghai, China
Liaoning Cancer Hospital & Institute, Shenyang, China
Beijing Chest Hospital, Capital Medical University, Beijing, China
The Second Affiliated Hospital of Kunming Medical University, Kunming, China
Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
He'nan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
The Second Xiangya Hospital of Central South University, Changsha, China
Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
Peking Union Medical College Hospital, Beijing, China
Peking University People's Hospital, Beijing, China
Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
Nanfang Hospital, Guangzhou, China
Tangdu Hospital, Air Force Military Medical University, Xi'an, China
The First People's Hospital of Foshan, Foshan, China
Daping Hospital of Army Medical University, Chongqing, China

Abstract

The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

Keywords: consensus, non‐small cell lung cancer, contention, uncommon/rare oncogenic drivers

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Publication history

Received: 08 October 2023
Accepted: 05 November 2023
Published: 12 December 2023
Issue date: December 2023

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© 2023 The Authors. Tsinghua University Press.

Acknowledgements

ACKNOWLEDGMENTS

Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (2017B030314120, Yi‐Long Wu), Guangdong Provincial Peoples Hospital Scientific Research Fundsfor Leading MedicalTalentsin Guangdong Province (KJ012019426, Yi‐Long Wu), the National Natural Science Foundation of China (Grant No.82072562, Qing Zhou).

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