Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients

Abstract Background There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M‐cis‐C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among t...

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Autores principales: Yaning Yang, Haiyan Xu, Li Ma, Lu Yang, Guangjian Yang, Shuyang Zhang, Xin Ai, Shucai Zhang, Yan Wang
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Publicado: Wiley 2021
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spelling oai:doaj.org-article:50fab161492a40c8bc3cf49fe03b35de2021-12-01T04:49:14ZPossibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients2045-763410.1002/cam4.4336https://doaj.org/article/50fab161492a40c8bc3cf49fe03b35de2021-12-01T00:00:00Zhttps://doi.org/10.1002/cam4.4336https://doaj.org/toc/2045-7634Abstract Background There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M‐cis‐C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients. Methods This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M‐cis‐C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib‐based therapy, 23 patients received chemotherapy in combination of anti‐angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs. Results Compared to other targeted therapy, brigatinib‐based therapy (median progression‐free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21–0.73, p = 0.001) and chemotherapy‐based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06–0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib‐based therapy and chemotherapy‐based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57–2.67, p = 0.58). Chemotherapy combined with anti‐angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11–0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06–0.54, p = 0.001), no matter they received brigatinib‐based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01–0.96, p = 0.05) or chemotherapy‐based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01–0.49, p < 0.001). Conclusion Brigatinib‐based therapy and chemotherapy plus anti‐angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis‐C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis‐C797S mutation.Yaning YangHaiyan XuLi MaLu YangGuangjian YangShuyang ZhangXin AiShucai ZhangYan WangWileyarticlecis‐C797SEGFRnon‐small cell lung cancerresistancetreatmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Medicine, Vol 10, Iss 23, Pp 8328-8337 (2021)
institution DOAJ
collection DOAJ
language EN
topic cis‐C797S
EGFR
non‐small cell lung cancer
resistance
treatment
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle cis‐C797S
EGFR
non‐small cell lung cancer
resistance
treatment
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Yaning Yang
Haiyan Xu
Li Ma
Lu Yang
Guangjian Yang
Shuyang Zhang
Xin Ai
Shucai Zhang
Yan Wang
Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients
description Abstract Background There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M‐cis‐C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients. Methods This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M‐cis‐C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib‐based therapy, 23 patients received chemotherapy in combination of anti‐angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs. Results Compared to other targeted therapy, brigatinib‐based therapy (median progression‐free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21–0.73, p = 0.001) and chemotherapy‐based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06–0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib‐based therapy and chemotherapy‐based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57–2.67, p = 0.58). Chemotherapy combined with anti‐angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11–0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06–0.54, p = 0.001), no matter they received brigatinib‐based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01–0.96, p = 0.05) or chemotherapy‐based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01–0.49, p < 0.001). Conclusion Brigatinib‐based therapy and chemotherapy plus anti‐angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis‐C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis‐C797S mutation.
format article
author Yaning Yang
Haiyan Xu
Li Ma
Lu Yang
Guangjian Yang
Shuyang Zhang
Xin Ai
Shucai Zhang
Yan Wang
author_facet Yaning Yang
Haiyan Xu
Li Ma
Lu Yang
Guangjian Yang
Shuyang Zhang
Xin Ai
Shucai Zhang
Yan Wang
author_sort Yaning Yang
title Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients
title_short Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients
title_full Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients
title_fullStr Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients
title_full_unstemmed Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients
title_sort possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring egfr t790m‐cis‐c797s mutations in lung adenocarcinoma patients
publisher Wiley
publishDate 2021
url https://doaj.org/article/50fab161492a40c8bc3cf49fe03b35de
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