{"title":"针对表皮生长因子受体 p.L861Q 突变的晚期 NSCLC,根据脑转移状态明确表皮生长因子受体-TKI 的选择。","authors":"","doi":"10.1016/j.neo.2024.101073","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>In-depth insight into the genomic features of the uncommon EGFR p.L861Q mutant NSCLC is scarcely performed, and no consensus on the preferred treatment strategy has been established. Moreover, the therapeutic implications of EGFR-TKI stratified by clinical and molecular features remained largely unknown.</div></div><div><h3>Methods</h3><div>A multi-center NGS database comprising 44,993 NSCLC samples was utilized for the genomic landscape profiling of EGFR p.L861Q mutation. Furthermore, a real-world cohort of 207 patients harboring EGFR p.L861Q mutation with complete treatment history was curated for comprehensive clinical analysis.</div></div><div><h3>Results</h3><div>L861Q is prevalent in approximately 2.1% of EGFR-mutated NSCLC and is typically co-mutated with EGFR p.G719X on the same allele (20%) and exhibits co-occurrent EGFR copy number amplification in approximately 17% of cases. In the first-line setting, afatinib and third-generation EGFR-TKI have been shown to yield notably superior treatment outcomes compared to first-generation EGFR-TKI (1<sup>st</sup> vs.2<sup>nd</sup> vs.3<sup>rd</sup> generations, ORR: 15.8% vs.56.5% vs.46.7%, <em>P</em>=0.01; median PFS: 6.4 vs.13.5 vs.15.1 months, <em>P</em>=0.002). This finding consistently held for patients without CNS metastases (1<sup>st</sup> vs.2<sup>nd</sup> vs.3<sup>rd</sup> generations, median PFS:6.0 vs.18.2 vs.14.1 months, <em>P</em>=0.003). In contrast, third-generation EGFR-TKI demonstrated superior efficacy compared to afatinib or first-generation TKI among the subgroup of brain metastasis (Pooled 1<sup>st</sup>/2<sup>nd</sup>-generation vs.3<sup>rd</sup>-generation TKI, brain ORR:0.00% vs.33.33%; median PFS:7.9 vs.19.3 months, <em>P</em>=0.021). Additional concurrent EGFR mutations or EGFR amplification did not yield a discernible impact on the efficacy of EGFR-TKI.</div></div><div><h3>Conclusions</h3><div>The present study comprehensively elucidates the molecular features of EGFR p.L861Q mutation and underscores the optimal therapeutic choice of first-line EGFR-TKI based on brain metastatic status.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Specifying the choice of EGFR-TKI based on brain metastatic status for advanced NSCLC with EGFR p.L861Q mutation\",\"authors\":\"\",\"doi\":\"10.1016/j.neo.2024.101073\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>In-depth insight into the genomic features of the uncommon EGFR p.L861Q mutant NSCLC is scarcely performed, and no consensus on the preferred treatment strategy has been established. Moreover, the therapeutic implications of EGFR-TKI stratified by clinical and molecular features remained largely unknown.</div></div><div><h3>Methods</h3><div>A multi-center NGS database comprising 44,993 NSCLC samples was utilized for the genomic landscape profiling of EGFR p.L861Q mutation. Furthermore, a real-world cohort of 207 patients harboring EGFR p.L861Q mutation with complete treatment history was curated for comprehensive clinical analysis.</div></div><div><h3>Results</h3><div>L861Q is prevalent in approximately 2.1% of EGFR-mutated NSCLC and is typically co-mutated with EGFR p.G719X on the same allele (20%) and exhibits co-occurrent EGFR copy number amplification in approximately 17% of cases. In the first-line setting, afatinib and third-generation EGFR-TKI have been shown to yield notably superior treatment outcomes compared to first-generation EGFR-TKI (1<sup>st</sup> vs.2<sup>nd</sup> vs.3<sup>rd</sup> generations, ORR: 15.8% vs.56.5% vs.46.7%, <em>P</em>=0.01; median PFS: 6.4 vs.13.5 vs.15.1 months, <em>P</em>=0.002). This finding consistently held for patients without CNS metastases (1<sup>st</sup> vs.2<sup>nd</sup> vs.3<sup>rd</sup> generations, median PFS:6.0 vs.18.2 vs.14.1 months, <em>P</em>=0.003). In contrast, third-generation EGFR-TKI demonstrated superior efficacy compared to afatinib or first-generation TKI among the subgroup of brain metastasis (Pooled 1<sup>st</sup>/2<sup>nd</sup>-generation vs.3<sup>rd</sup>-generation TKI, brain ORR:0.00% vs.33.33%; median PFS:7.9 vs.19.3 months, <em>P</em>=0.021). Additional concurrent EGFR mutations or EGFR amplification did not yield a discernible impact on the efficacy of EGFR-TKI.</div></div><div><h3>Conclusions</h3><div>The present study comprehensively elucidates the molecular features of EGFR p.L861Q mutation and underscores the optimal therapeutic choice of first-line EGFR-TKI based on brain metastatic status.</div></div>\",\"PeriodicalId\":18917,\"journal\":{\"name\":\"Neoplasia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-10-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neoplasia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1476558624001143\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neoplasia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1476558624001143","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Specifying the choice of EGFR-TKI based on brain metastatic status for advanced NSCLC with EGFR p.L861Q mutation
Background
In-depth insight into the genomic features of the uncommon EGFR p.L861Q mutant NSCLC is scarcely performed, and no consensus on the preferred treatment strategy has been established. Moreover, the therapeutic implications of EGFR-TKI stratified by clinical and molecular features remained largely unknown.
Methods
A multi-center NGS database comprising 44,993 NSCLC samples was utilized for the genomic landscape profiling of EGFR p.L861Q mutation. Furthermore, a real-world cohort of 207 patients harboring EGFR p.L861Q mutation with complete treatment history was curated for comprehensive clinical analysis.
Results
L861Q is prevalent in approximately 2.1% of EGFR-mutated NSCLC and is typically co-mutated with EGFR p.G719X on the same allele (20%) and exhibits co-occurrent EGFR copy number amplification in approximately 17% of cases. In the first-line setting, afatinib and third-generation EGFR-TKI have been shown to yield notably superior treatment outcomes compared to first-generation EGFR-TKI (1st vs.2nd vs.3rd generations, ORR: 15.8% vs.56.5% vs.46.7%, P=0.01; median PFS: 6.4 vs.13.5 vs.15.1 months, P=0.002). This finding consistently held for patients without CNS metastases (1st vs.2nd vs.3rd generations, median PFS:6.0 vs.18.2 vs.14.1 months, P=0.003). In contrast, third-generation EGFR-TKI demonstrated superior efficacy compared to afatinib or first-generation TKI among the subgroup of brain metastasis (Pooled 1st/2nd-generation vs.3rd-generation TKI, brain ORR:0.00% vs.33.33%; median PFS:7.9 vs.19.3 months, P=0.021). Additional concurrent EGFR mutations or EGFR amplification did not yield a discernible impact on the efficacy of EGFR-TKI.
Conclusions
The present study comprehensively elucidates the molecular features of EGFR p.L861Q mutation and underscores the optimal therapeutic choice of first-line EGFR-TKI based on brain metastatic status.
期刊介绍:
Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.