Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M

Abstract Background In the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yurong Wang, Ruipan Zheng, Peizhu Hu, Ziheng Zhang, Shujing Shen, Xingya Li
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	EGFR exon 19 deletion-insertion EGFR TKI Clinical outcomes Resistance mechanism NSCLC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f563a95006724209905667bab22efc65
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f563a95006724209905667bab22efc65
record_format	dspace
spelling	oai:doaj.org-article:f563a95006724209905667bab22efc652021-11-14T12:30:43ZPatients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M10.1186/s12885-021-08942-x1471-2407https://doaj.org/article/f563a95006724209905667bab22efc652021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08942-xhttps://doaj.org/toc/1471-2407Abstract Background In the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the similar responses and resistant mechanisms to first-generation EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients. Methods We successively and retrospectively reviewed the NGS data of 3054 patients diagnosed as advanced NSCLC from November 2017 to September 2020. Finally, 41 patients with EGFR 19delins mutation and 41 patients with EGFR 19del mutation who received first-generation EGFR TKIs as first-line therapy were included in the study. Results A total of 17 genotypes were identified in this study, including L747_P753delinsS (10/41), L747_A750delinsP (9/41), L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, the population of EGFR 19delins respond well to first line EGFR TKIs as well as those of EGFR 19del, with little difference in median progression-free survival (mPFS): 10.4 months vs. 13.1 months, p = 0.1076). Interestingly, patients with L747_T751delinsP seem to have a better mPFS than others (18.7 months vs. 13.1 months, p = 0.035). After the disease progression, both EGFR 19delins and EGFR 19del had similar rates of developing EGFR T790M mutation resistance (45.8% vs. 57.8%), and those receiving osimeritinib as second-line treatment obtain the similar survival benefits (mPFS: 12.0 months vs. 12.2 months (p = 0.97). Conclusions This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.Yurong WangRuipan ZhengPeizhu HuZiheng ZhangShujing ShenXingya LiBMCarticleEGFR exon 19 deletion-insertionEGFR TKIClinical outcomesResistance mechanismNSCLCNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EGFR exon 19 deletion-insertion EGFR TKI Clinical outcomes Resistance mechanism NSCLC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	EGFR exon 19 deletion-insertion EGFR TKI Clinical outcomes Resistance mechanism NSCLC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yurong Wang Ruipan Zheng Peizhu Hu Ziheng Zhang Shujing Shen Xingya Li Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M
description	Abstract Background In the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the similar responses and resistant mechanisms to first-generation EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients. Methods We successively and retrospectively reviewed the NGS data of 3054 patients diagnosed as advanced NSCLC from November 2017 to September 2020. Finally, 41 patients with EGFR 19delins mutation and 41 patients with EGFR 19del mutation who received first-generation EGFR TKIs as first-line therapy were included in the study. Results A total of 17 genotypes were identified in this study, including L747_P753delinsS (10/41), L747_A750delinsP (9/41), L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, the population of EGFR 19delins respond well to first line EGFR TKIs as well as those of EGFR 19del, with little difference in median progression-free survival (mPFS): 10.4 months vs. 13.1 months, p = 0.1076). Interestingly, patients with L747_T751delinsP seem to have a better mPFS than others (18.7 months vs. 13.1 months, p = 0.035). After the disease progression, both EGFR 19delins and EGFR 19del had similar rates of developing EGFR T790M mutation resistance (45.8% vs. 57.8%), and those receiving osimeritinib as second-line treatment obtain the similar survival benefits (mPFS: 12.0 months vs. 12.2 months (p = 0.97). Conclusions This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.
format	article
author	Yurong Wang Ruipan Zheng Peizhu Hu Ziheng Zhang Shujing Shen Xingya Li
author_facet	Yurong Wang Ruipan Zheng Peizhu Hu Ziheng Zhang Shujing Shen Xingya Li
author_sort	Yurong Wang
title	Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M
title_short	Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M
title_full	Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M
title_fullStr	Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M
title_full_unstemmed	Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M
title_sort	patients harboring uncommon egfr exon 19 deletion-insertion mutations respond well to first-generation egfr inhibitors and osimeritinib upon acquisition of t790m
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f563a95006724209905667bab22efc65
work_keys_str_mv	AT yurongwang patientsharboringuncommonegfrexon19deletioninsertionmutationsrespondwelltofirstgenerationegfrinhibitorsandosimeritinibuponacquisitionoft790m AT ruipanzheng patientsharboringuncommonegfrexon19deletioninsertionmutationsrespondwelltofirstgenerationegfrinhibitorsandosimeritinibuponacquisitionoft790m AT peizhuhu patientsharboringuncommonegfrexon19deletioninsertionmutationsrespondwelltofirstgenerationegfrinhibitorsandosimeritinibuponacquisitionoft790m AT zihengzhang patientsharboringuncommonegfrexon19deletioninsertionmutationsrespondwelltofirstgenerationegfrinhibitorsandosimeritinibuponacquisitionoft790m AT shujingshen patientsharboringuncommonegfrexon19deletioninsertionmutationsrespondwelltofirstgenerationegfrinhibitorsandosimeritinibuponacquisitionoft790m AT xingyali patientsharboringuncommonegfrexon19deletioninsertionmutationsrespondwelltofirstgenerationegfrinhibitorsandosimeritinibuponacquisitionoft790m
_version_	1718429204124532736

Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M

Ejemplares similares