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Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials

BACKGROUND: Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The...

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Autores principales: Mao, Shiqi, Yang, Shuo, Liu, Xinyu, Li, Xingya, Wang, Qiming, Zhang, Yiping, Chen, Jianhua, Wang, Yan, Gao, Guanghui, Wu, Fengying, Jiang, Tao, Zhang, Jiao, Yang, Ying, Lin, Xiang, Zhu, Xiaoyu, Zhou, Caicun, Ren, Shengxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251549/
https://www.ncbi.nlm.nih.gov/pubmed/37296463
http://dx.doi.org/10.1186/s40164-023-00417-y
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author Mao, Shiqi
Yang, Shuo
Liu, Xinyu
Li, Xingya
Wang, Qiming
Zhang, Yiping
Chen, Jianhua
Wang, Yan
Gao, Guanghui
Wu, Fengying
Jiang, Tao
Zhang, Jiao
Yang, Ying
Lin, Xiang
Zhu, Xiaoyu
Zhou, Caicun
Ren, Shengxiang
author_facet Mao, Shiqi
Yang, Shuo
Liu, Xinyu
Li, Xingya
Wang, Qiming
Zhang, Yiping
Chen, Jianhua
Wang, Yan
Gao, Guanghui
Wu, Fengying
Jiang, Tao
Zhang, Jiao
Yang, Ying
Lin, Xiang
Zhu, Xiaoyu
Zhou, Caicun
Ren, Shengxiang
author_sort Mao, Shiqi
collection PubMed
description BACKGROUND: Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation. METHODS: Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated. RESULTS: This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not. CONCLUSION: Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting. Trial registration: The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40164-023-00417-y.
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spelling pubmed-102515492023-06-10 Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials Mao, Shiqi Yang, Shuo Liu, Xinyu Li, Xingya Wang, Qiming Zhang, Yiping Chen, Jianhua Wang, Yan Gao, Guanghui Wu, Fengying Jiang, Tao Zhang, Jiao Yang, Ying Lin, Xiang Zhu, Xiaoyu Zhou, Caicun Ren, Shengxiang Exp Hematol Oncol Research BACKGROUND: Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation. METHODS: Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated. RESULTS: This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not. CONCLUSION: Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting. Trial registration: The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40164-023-00417-y. BioMed Central 2023-06-09 /pmc/articles/PMC10251549/ /pubmed/37296463 http://dx.doi.org/10.1186/s40164-023-00417-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mao, Shiqi
Yang, Shuo
Liu, Xinyu
Li, Xingya
Wang, Qiming
Zhang, Yiping
Chen, Jianhua
Wang, Yan
Gao, Guanghui
Wu, Fengying
Jiang, Tao
Zhang, Jiao
Yang, Ying
Lin, Xiang
Zhu, Xiaoyu
Zhou, Caicun
Ren, Shengxiang
Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
title Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
title_full Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
title_fullStr Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
title_full_unstemmed Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
title_short Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
title_sort molecular correlation of response to pyrotinib in advanced nsclc with her2 mutation: biomarker analysis from two phase ii trials
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251549/
https://www.ncbi.nlm.nih.gov/pubmed/37296463
http://dx.doi.org/10.1186/s40164-023-00417-y
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