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Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations

BACKGROUND: To characterize the effects of mutation subtypes and concomitant pathogenic mutations on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations tr...

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Autores principales: Wang, Yue, Li, Jingwen, Zhou, Yan, Cao, Shuhui, Ling, Xuxinyi, Zhang, Yao, Nie, Wei, Zhong, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661900/
https://www.ncbi.nlm.nih.gov/pubmed/33209877
http://dx.doi.org/10.21037/atm-20-6172
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author Wang, Yue
Li, Jingwen
Zhou, Yan
Cao, Shuhui
Ling, Xuxinyi
Zhang, Yao
Nie, Wei
Zhong, Hua
author_facet Wang, Yue
Li, Jingwen
Zhou, Yan
Cao, Shuhui
Ling, Xuxinyi
Zhang, Yao
Nie, Wei
Zhong, Hua
author_sort Wang, Yue
collection PubMed
description BACKGROUND: To characterize the effects of mutation subtypes and concomitant pathogenic mutations on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations treated with chemotherapy. METHODS: We retrospectively found that patients who underwent genomic analysis from January 2017 to December 2019, and 101 patients with advanced EGFR ex20ins NSCLC were found. Binary logistic regression and Cox regression were used to determine how EGFR ex20ins mutation subtypes and concomitant mutations are associated with PFS and OS. RESULTS: A total of 8,348 patients were screened and 101 advanced EGFR ex20ins NSCLC patients were detected. Fifty-five patients who received chemotherapy (n=49) or TKIs (n=6) as first-line treatment were recorded for PFS and OS. PFS and OS were significantly longer in the platinum-based chemotherapy group (median PFS: 7.6 versus 5.6 months; P=0.001; median OS: 19.9 versus 7.4 months; P=0.027) than in the TKI group. Common mutations include Ala767_Val769dupAlaSerVal (A767_V769dupASV), Ser768_Asp770dupSerValAsp (S768_D770dupSVD) and Ala763_Tyr764insPheGlnGluAla (A763_Y764insFQEA). On binary logistic regression, common mutations (OR =17.04, 95% CI: 1.39–209.56; P=0.027) and number of concomitant mutations ≤1 (OR =34.67, 95% CI: 2.02–595.48; P=0.015) is significantly associated with durable clinical benefit (DCB). On multivariable analysis, common mutations (HR =0.26, 95% CI: 0.0.10–0.63; P=0.003) and the number of concomitant mutations ≤1 (HR =0.33, 95% CI: 0.15–0.73; P=0.006) were significantly associated with longer PFS. CONCLUSIONS: Common mutations and the number of concomitant mutations ≤1 correlate with a biomarker that predicts benefit from chemotherapy and confers excellent prognosis for advanced patients with advanced EGFR ex20ins NSCLC. Patients with common mutations and with only one concomitant mutation had the greatest PFS and patients with uncommon mutations, and with over one concomitant mutation had the worst prognosis.
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spelling pubmed-76619002020-11-17 Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations Wang, Yue Li, Jingwen Zhou, Yan Cao, Shuhui Ling, Xuxinyi Zhang, Yao Nie, Wei Zhong, Hua Ann Transl Med Original Article BACKGROUND: To characterize the effects of mutation subtypes and concomitant pathogenic mutations on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations treated with chemotherapy. METHODS: We retrospectively found that patients who underwent genomic analysis from January 2017 to December 2019, and 101 patients with advanced EGFR ex20ins NSCLC were found. Binary logistic regression and Cox regression were used to determine how EGFR ex20ins mutation subtypes and concomitant mutations are associated with PFS and OS. RESULTS: A total of 8,348 patients were screened and 101 advanced EGFR ex20ins NSCLC patients were detected. Fifty-five patients who received chemotherapy (n=49) or TKIs (n=6) as first-line treatment were recorded for PFS and OS. PFS and OS were significantly longer in the platinum-based chemotherapy group (median PFS: 7.6 versus 5.6 months; P=0.001; median OS: 19.9 versus 7.4 months; P=0.027) than in the TKI group. Common mutations include Ala767_Val769dupAlaSerVal (A767_V769dupASV), Ser768_Asp770dupSerValAsp (S768_D770dupSVD) and Ala763_Tyr764insPheGlnGluAla (A763_Y764insFQEA). On binary logistic regression, common mutations (OR =17.04, 95% CI: 1.39–209.56; P=0.027) and number of concomitant mutations ≤1 (OR =34.67, 95% CI: 2.02–595.48; P=0.015) is significantly associated with durable clinical benefit (DCB). On multivariable analysis, common mutations (HR =0.26, 95% CI: 0.0.10–0.63; P=0.003) and the number of concomitant mutations ≤1 (HR =0.33, 95% CI: 0.15–0.73; P=0.006) were significantly associated with longer PFS. CONCLUSIONS: Common mutations and the number of concomitant mutations ≤1 correlate with a biomarker that predicts benefit from chemotherapy and confers excellent prognosis for advanced patients with advanced EGFR ex20ins NSCLC. Patients with common mutations and with only one concomitant mutation had the greatest PFS and patients with uncommon mutations, and with over one concomitant mutation had the worst prognosis. AME Publishing Company 2020-10 /pmc/articles/PMC7661900/ /pubmed/33209877 http://dx.doi.org/10.21037/atm-20-6172 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Wang, Yue
Li, Jingwen
Zhou, Yan
Cao, Shuhui
Ling, Xuxinyi
Zhang, Yao
Nie, Wei
Zhong, Hua
Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations
title Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations
title_full Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations
title_fullStr Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations
title_full_unstemmed Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations
title_short Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations
title_sort tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661900/
https://www.ncbi.nlm.nih.gov/pubmed/33209877
http://dx.doi.org/10.21037/atm-20-6172
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