{"doi":"10.1002/1878-0261.13439","title":"Genomic and immune characteristics of <i>HER2</i>‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy","abstract":"<jats:p>The efficacy of immunotherapy in advanced <jats:italic>HER2</jats:italic>‐mutated non‐small‐cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with <jats:italic>de novo HER2</jats:italic> 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, <jats:italic>n</jats:italic> = 21; META‐ICI, <jats:italic>n</jats:italic> = 30) were used for validation. In the GLCI cohort, 68.2% of patients displayed programmed death‐ligand 1 (PD‐L1) expression &lt; 1%. Compared with ex20ins patients, non‐ex20ins patients had more concurrent mutations in the GLCI cohort (<jats:italic>P</jats:italic> &lt; 0.01) and a higher tumour mutation burden in the TCGA cohort (<jats:italic>P</jats:italic> = 0.03). Under ICI‐based therapy, advanced NSCLC patients with non‐ex20ins had potentially superior progression‐free survival [median: 13.0 <jats:italic>vs</jats:italic>. 3.6 months, adjusted hazard ratio (HR): 0.31, 95% confidence interval (CI): 0.11–0.83] and overall survival (median: 27.5 <jats:italic>vs.</jats:italic> 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 <jats:italic>HER2</jats:italic>‐mutated NSCLC, with potentially better efficacy in non‐ex20ins patients. Further investigations are warranted in clinical practice.</jats:p>","journal":"Molecular Oncology","year":2023,"id":624150,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1377226,"name":"Kai Yin","orcid":"0000-0001-8802-766X","position":1,"is_corresponding":false},{"id":1551827,"name":"Xiaotian Zhao","orcid":"0000-0003-3823-3232","position":2,"is_corresponding":false},{"id":1613326,"name":"E‐E Ke","orcid":null,"position":3,"is_corresponding":false},{"id":1613327,"name":"Si‐Pei Wu","orcid":null,"position":4,"is_corresponding":false},{"id":1613328,"name":"Yang‐Si Li","orcid":null,"position":5,"is_corresponding":false},{"id":1613329,"name":"Mei‐Mei Zheng","orcid":null,"position":6,"is_corresponding":false},{"id":1268446,"name":"Si‐Yang Maggie Liu","orcid":"0000-0002-3837-0758","position":7,"is_corresponding":false},{"id":235751,"name":"Chong‐Rui Xu","orcid":"0000-0002-3474-2809","position":8,"is_corresponding":false},{"id":1613330,"name":"Yue‐Li Sun","orcid":null,"position":9,"is_corresponding":false},{"id":1613331,"name":"Jia‐Xin Lin","orcid":null,"position":10,"is_corresponding":false},{"id":1613332,"name":"Xiao‐Yan Bai","orcid":null,"position":11,"is_corresponding":false},{"id":1613333,"name":"Yi‐Chen Zhang","orcid":null,"position":12,"is_corresponding":false},{"id":888284,"name":"Qing Zhou","orcid":"0000-0003-2565-3721","position":13,"is_corresponding":false},{"id":1613334,"name":"Jin‐Ji Yang","orcid":"0000-0002-8498-0119","position":14,"is_corresponding":false},{"id":1377230,"name":"Wen‐Zhao Zhong","orcid":"0000-0002-8917-8635","position":15,"is_corresponding":false},{"id":1613335,"name":"Bing‐Chao Wang","orcid":null,"position":16,"is_corresponding":false},{"id":1024296,"name":"Xu‐Chao Zhang","orcid":"0000-0002-4138-8115","position":17,"is_corresponding":false},{"id":592807,"name":"Dongqin Zhu","orcid":null,"position":18,"is_corresponding":false},{"id":458879,"name":"Lingling Yang","orcid":"0000-0002-0976-2090","position":19,"is_corresponding":false},{"id":1551829,"name":"Qiuxiang Ou","orcid":"0000-0002-2961-2057","position":20,"is_corresponding":false},{"id":498896,"name":"Yi‐Long Wu","orcid":"0000-0002-3611-0258","position":21,"is_corresponding":false},{"id":235749,"name":"Hai‐Yan Tu","orcid":"0000-0001-7125-9878","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Genomic and immune characteristics of <i>HER2</i>‐mutated non‐small‐cell lung cancer and response to immune checkpoint inhibitor‐based therapy","abstract":"<jats:p>The efficacy of immunotherapy in advanced <jats:italic>HER2</jats:italic>‐mutated non‐small‐cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with <jats:italic>de novo HER2</jats:italic> 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, <jats:italic>n</jats:italic> = 21; META‐ICI, <jats:italic>n</jats:italic> = 30) were used for validation. In the GLCI cohort, 68.2% of patients displayed programmed death‐ligand 1 (PD‐L1) expression &lt; 1%. Compared with ex20ins patients, non‐ex20ins patients had more concurrent mutations in the GLCI cohort (<jats:italic>P</jats:italic> &lt; 0.01) and a higher tumour mutation burden in the TCGA cohort (<jats:italic>P</jats:italic> = 0.03). Under ICI‐based therapy, advanced NSCLC patients with non‐ex20ins had potentially superior progression‐free survival [median: 13.0 <jats:italic>vs</jats:italic>. 3.6 months, adjusted hazard ratio (HR): 0.31, 95% confidence interval (CI): 0.11–0.83] and overall survival (median: 27.5 <jats:italic>vs.</jats:italic> 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 <jats:italic>HER2</jats:italic>‐mutated NSCLC, with potentially better efficacy in non‐ex20ins patients. 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