Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy
The efficacy of immunotherapy in advanced HER2‐mutated non‐small‐cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with de novo HER2 mutations were retrospectively studied at Guangdong Lung Cancer Institute [GLCI cohort, exon 20 insertions (ex20ins): 71.0%] to...
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13439 |
| _version_ | 1827878136137646080 |
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| author | Hai‐Yan Tu Kai Yin Xiaotian Zhao E‐E Ke Si‐Pei Wu Yang‐Si Li Mei‐Mei Zheng Si‐Yang Maggie Liu Chong‐Rui Xu Yue‐Li Sun Jia‐Xin Lin Xiao‐Yan Bai Yi‐Chen Zhang Qing Zhou Jin‐Ji Yang Wen‐Zhao Zhong Bing‐Chao Wang Xu‐Chao Zhang Dongqin Zhu Lingling Yang Qiuxiang Ou Yi‐Long Wu |
| author_facet | Hai‐Yan Tu Kai Yin Xiaotian Zhao E‐E Ke Si‐Pei Wu Yang‐Si Li Mei‐Mei Zheng Si‐Yang Maggie Liu Chong‐Rui Xu Yue‐Li Sun Jia‐Xin Lin Xiao‐Yan Bai Yi‐Chen Zhang Qing Zhou Jin‐Ji Yang Wen‐Zhao Zhong Bing‐Chao Wang Xu‐Chao Zhang Dongqin Zhu Lingling Yang Qiuxiang Ou Yi‐Long Wu |
| author_sort | Hai‐Yan Tu |
| collection | DOAJ |
| description | The efficacy of immunotherapy in advanced HER2‐mutated non‐small‐cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with de novo HER2 mutations were retrospectively studied at Guangdong Lung Cancer Institute [GLCI cohort, exon 20 insertions (ex20ins): 71.0%] to compare clinical/molecular features and immune checkpoint inhibitor (ICI)‐based therapy efficacy between patients with ex20ins and non‐ex20ins. Two external cohorts (TCGA, n = 21; META‐ICI, n = 30) were used for validation. In the GLCI cohort, 68.2% of patients displayed programmed death‐ligand 1 (PD‐L1) expression < 1%. Compared with ex20ins patients, non‐ex20ins patients had more concurrent mutations in the GLCI cohort (P < 0.01) and a higher tumour mutation burden in the TCGA cohort (P = 0.03). Under ICI‐based therapy, advanced NSCLC patients with non‐ex20ins had potentially superior progression‐free survival [median: 13.0 vs. 3.6 months, adjusted hazard ratio (HR): 0.31, 95% confidence interval (CI): 0.11–0.83] and overall survival (median: 27.5 vs. 8.1 months, adjusted HR: 0.39, 95% CI: 0.13–1.18) to ex20ins patients, consistent with findings in the META‐ICI cohort. ICI‐based therapy may serve as an option for advanced HER2‐mutated NSCLC, with potentially better efficacy in non‐ex20ins patients. Further investigations are warranted in clinical practice. |
| first_indexed | 2024-03-12T17:46:59Z |
| format | Article |
| id | doaj.art-d5aadd22e14b45079cd59c661d0f474c |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-12T17:46:59Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-d5aadd22e14b45079cd59c661d0f474c2023-08-03T16:44:14ZengWileyMolecular Oncology1574-78911878-02612023-08-011781581159410.1002/1878-0261.13439Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapyHai‐Yan Tu0Kai Yin1Xiaotian Zhao2E‐E Ke3Si‐Pei Wu4Yang‐Si Li5Mei‐Mei Zheng6Si‐Yang Maggie Liu7Chong‐Rui Xu8Yue‐Li Sun9Jia‐Xin Lin10Xiao‐Yan Bai11Yi‐Chen Zhang12Qing Zhou13Jin‐Ji Yang14Wen‐Zhao Zhong15Bing‐Chao Wang16Xu‐Chao Zhang17Dongqin Zhu18Lingling Yang19Qiuxiang Ou20Yi‐Long Wu21Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGeneseeq Research Institute Nanjing Geneseeq Technology Inc. ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Medical Research Center Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaDepartment of Hematology, First Affiliated Hospital, Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education Jinan University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaThe Second School of Clinical Medicine Southern Medical University Guangzhou ChinaGeneseeq Research Institute Nanjing Geneseeq Technology Inc. ChinaGeneseeq Research Institute Nanjing Geneseeq Technology Inc. ChinaGeneseeq Research Institute Nanjing Geneseeq Technology Inc. ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou ChinaThe efficacy of immunotherapy in advanced HER2‐mutated non‐small‐cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with de novo HER2 mutations were retrospectively studied at Guangdong Lung Cancer Institute [GLCI cohort, exon 20 insertions (ex20ins): 71.0%] to compare clinical/molecular features and immune checkpoint inhibitor (ICI)‐based therapy efficacy between patients with ex20ins and non‐ex20ins. Two external cohorts (TCGA, n = 21; META‐ICI, n = 30) were used for validation. In the GLCI cohort, 68.2% of patients displayed programmed death‐ligand 1 (PD‐L1) expression < 1%. Compared with ex20ins patients, non‐ex20ins patients had more concurrent mutations in the GLCI cohort (P < 0.01) and a higher tumour mutation burden in the TCGA cohort (P = 0.03). Under ICI‐based therapy, advanced NSCLC patients with non‐ex20ins had potentially superior progression‐free survival [median: 13.0 vs. 3.6 months, adjusted hazard ratio (HR): 0.31, 95% confidence interval (CI): 0.11–0.83] and overall survival (median: 27.5 vs. 8.1 months, adjusted HR: 0.39, 95% CI: 0.13–1.18) to ex20ins patients, consistent with findings in the META‐ICI cohort. ICI‐based therapy may serve as an option for advanced HER2‐mutated NSCLC, with potentially better efficacy in non‐ex20ins patients. Further investigations are warranted in clinical practice.https://doi.org/10.1002/1878-0261.13439advanced NSCLCexon 20 insertionhuman epidermal growth factor receptor 2immune checkpoint inhibitornon‐exon 20 insertion |
| spellingShingle | Hai‐Yan Tu Kai Yin Xiaotian Zhao E‐E Ke Si‐Pei Wu Yang‐Si Li Mei‐Mei Zheng Si‐Yang Maggie Liu Chong‐Rui Xu Yue‐Li Sun Jia‐Xin Lin Xiao‐Yan Bai Yi‐Chen Zhang Qing Zhou Jin‐Ji Yang Wen‐Zhao Zhong Bing‐Chao Wang Xu‐Chao Zhang Dongqin Zhu Lingling Yang Qiuxiang Ou Yi‐Long Wu Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy Molecular Oncology advanced NSCLC exon 20 insertion human epidermal growth factor receptor 2 immune checkpoint inhibitor non‐exon 20 insertion |
| title | Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy |
| title_full | Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy |
| title_fullStr | Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy |
| title_full_unstemmed | Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy |
| title_short | Genomic and immune characteristics of HER2‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy |
| title_sort | genomic and immune characteristics of her2 mutated non small cell lung cancer and response to immune checkpoint inhibitor based therapy |
| topic | advanced NSCLC exon 20 insertion human epidermal growth factor receptor 2 immune checkpoint inhibitor non‐exon 20 insertion |
| url | https://doi.org/10.1002/1878-0261.13439 |
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