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A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report

Osimertinib has efficacy superior to that of standard epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for the first-line treatment of patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, patients treated with osimertinib eventually acquire drug re...

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Autores principales: Kuang, Yukun, Wang, Jiyu, Xu, Peihang, Zheng, Yifan, Bai, Lihong, Sun, Xue, Li, Zimu, Gan, Runjing, Li, Huixia, Ke, Zunfu, Tang, Kejing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422132/
https://www.ncbi.nlm.nih.gov/pubmed/34532491
http://dx.doi.org/10.21037/atm-21-3861
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author Kuang, Yukun
Wang, Jiyu
Xu, Peihang
Zheng, Yifan
Bai, Lihong
Sun, Xue
Li, Zimu
Gan, Runjing
Li, Huixia
Ke, Zunfu
Tang, Kejing
author_facet Kuang, Yukun
Wang, Jiyu
Xu, Peihang
Zheng, Yifan
Bai, Lihong
Sun, Xue
Li, Zimu
Gan, Runjing
Li, Huixia
Ke, Zunfu
Tang, Kejing
author_sort Kuang, Yukun
collection PubMed
description Osimertinib has efficacy superior to that of standard epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for the first-line treatment of patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, patients treated with osimertinib eventually acquire drug resistance. MET missense mutations have been demonstrated to mediate resistance to MET-TKIs, such as crizotinib. But the role of MET missense mutations in mediating EGFR TKI resistance is undefined. With the increasing use of next-generation sequencing (NGS) at diagnosis, many mechanisms of acquired resistance have been discovered in patients with activated tyrosine kinase receptors. Herein, we report the first case of MET D1228N mutation mediating acquired resistance to osimertinib in a MET TKI-naïve NSCLC. The patient with advanced lung adenocarcinoma harboring EGFR exon 19 deletion initially responded to osimertinib with progression-free survival (PFS) lasting 11 months and then developed resistance with an acquired mutation of MET D1228N. Subsequently, combination therapy of cabozantinib and osimertinib was administrated to the patient, and her clinical symptoms were rapidly relieved within one week with good tolerance. She remained on the combined treatment for 10 months. Finally, she achieved an overall survival (OS) of 25 months. Based on our findings, patient with MET D1228N mutant lung adenocarcinoma clinically benefited from combinatorial therapy of cabozantinib and osimertinib after osimertinib resistance.
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spelling pubmed-84221322021-09-15 A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report Kuang, Yukun Wang, Jiyu Xu, Peihang Zheng, Yifan Bai, Lihong Sun, Xue Li, Zimu Gan, Runjing Li, Huixia Ke, Zunfu Tang, Kejing Ann Transl Med Case Report Osimertinib has efficacy superior to that of standard epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for the first-line treatment of patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, patients treated with osimertinib eventually acquire drug resistance. MET missense mutations have been demonstrated to mediate resistance to MET-TKIs, such as crizotinib. But the role of MET missense mutations in mediating EGFR TKI resistance is undefined. With the increasing use of next-generation sequencing (NGS) at diagnosis, many mechanisms of acquired resistance have been discovered in patients with activated tyrosine kinase receptors. Herein, we report the first case of MET D1228N mutation mediating acquired resistance to osimertinib in a MET TKI-naïve NSCLC. The patient with advanced lung adenocarcinoma harboring EGFR exon 19 deletion initially responded to osimertinib with progression-free survival (PFS) lasting 11 months and then developed resistance with an acquired mutation of MET D1228N. Subsequently, combination therapy of cabozantinib and osimertinib was administrated to the patient, and her clinical symptoms were rapidly relieved within one week with good tolerance. She remained on the combined treatment for 10 months. Finally, she achieved an overall survival (OS) of 25 months. Based on our findings, patient with MET D1228N mutant lung adenocarcinoma clinically benefited from combinatorial therapy of cabozantinib and osimertinib after osimertinib resistance. AME Publishing Company 2021-08 /pmc/articles/PMC8422132/ /pubmed/34532491 http://dx.doi.org/10.21037/atm-21-3861 Text en 2021 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 Case Report
Kuang, Yukun
Wang, Jiyu
Xu, Peihang
Zheng, Yifan
Bai, Lihong
Sun, Xue
Li, Zimu
Gan, Runjing
Li, Huixia
Ke, Zunfu
Tang, Kejing
A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report
title A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report
title_full A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report
title_fullStr A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report
title_full_unstemmed A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report
title_short A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report
title_sort rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with met d1228n mutation: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422132/
https://www.ncbi.nlm.nih.gov/pubmed/34532491
http://dx.doi.org/10.21037/atm-21-3861
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