Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib

Rohit K Jain, Hongbin Chen Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA Abstract: In the last decade, there have been major therapeutic advances in the management of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. Crizotinib was...

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Autores principales:	Jain RK, Chen H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	non-small cell lung cancer ALK rearrangement crizotinib ceritinib alectinib brigatinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/58f4ee66587b41adbd8b14a79bca7393
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spelling	oai:doaj.org-article:58f4ee66587b41adbd8b14a79bca73932021-12-02T00:38:49ZSpotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib1179-2728https://doaj.org/article/58f4ee66587b41adbd8b14a79bca73932017-10-01T00:00:00Zhttps://www.dovepress.com/spotlight-on-brigatinib-and-its-potential-in-the-treatment-of-patients-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Rohit K Jain, Hongbin Chen Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA Abstract: In the last decade, there have been major therapeutic advances in the management of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. Crizotinib was the first approved ALK inhibitor with significant benefits over chemotherapy. However, patients inevitably develop disease progression especially in central nervous system and acquire resistance to crizotinib. Several next-generation ALK inhibitors have been developed to overcome these resistance mechanisms and have demonstrated clinical benefits in crizotinib-refractory non-small cell lung cancer including in central nervous system. Brigatinib is a second-generation ALK inhibitor with high level of activity against ALK and several other targets. It is active in vitro against many ALK kinase domain mutations including L1196M, E1210K, and G1202R which may mediate acquired resistance to other ALK inhibitors. In Phase I/II and ALTA clinical studies, brigatinib has demonstrated substantial and durable responses and intracranial responses after progression on crizotinib. It has acceptable safety profile, but early pulmonary toxicity has been observed prompting to pursue daily dosing of 180 mg (with lead-in). Overall, 180 mg (with lead-in) has showed consistently better efficacy than 90 mg. In this review, we will discuss in detail these two pivotal trials that led to the accelerated approval for brigatinib and its future directions. Keywords: non-small cell lung cancer, ALK rearrangement, crizotinib, ceritinib, alectinib, brigatinibJain RKChen HDove Medical Pressarticlenon-small cell lung cancerALK rearrangementcrizotinibceritinibalectinibbrigatinibNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 8, Pp 169-177 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-small cell lung cancer ALK rearrangement crizotinib ceritinib alectinib brigatinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	non-small cell lung cancer ALK rearrangement crizotinib ceritinib alectinib brigatinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jain RK Chen H Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib
description	Rohit K Jain, Hongbin Chen Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA Abstract: In the last decade, there have been major therapeutic advances in the management of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. Crizotinib was the first approved ALK inhibitor with significant benefits over chemotherapy. However, patients inevitably develop disease progression especially in central nervous system and acquire resistance to crizotinib. Several next-generation ALK inhibitors have been developed to overcome these resistance mechanisms and have demonstrated clinical benefits in crizotinib-refractory non-small cell lung cancer including in central nervous system. Brigatinib is a second-generation ALK inhibitor with high level of activity against ALK and several other targets. It is active in vitro against many ALK kinase domain mutations including L1196M, E1210K, and G1202R which may mediate acquired resistance to other ALK inhibitors. In Phase I/II and ALTA clinical studies, brigatinib has demonstrated substantial and durable responses and intracranial responses after progression on crizotinib. It has acceptable safety profile, but early pulmonary toxicity has been observed prompting to pursue daily dosing of 180 mg (with lead-in). Overall, 180 mg (with lead-in) has showed consistently better efficacy than 90 mg. In this review, we will discuss in detail these two pivotal trials that led to the accelerated approval for brigatinib and its future directions. Keywords: non-small cell lung cancer, ALK rearrangement, crizotinib, ceritinib, alectinib, brigatinib
format	article
author	Jain RK Chen H
author_facet	Jain RK Chen H
author_sort	Jain RK
title	Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib
title_short	Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib
title_full	Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib
title_fullStr	Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib
title_full_unstemmed	Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib
title_sort	spotlight on brigatinib and its potential in the treatment of patients with metastatic alk-positive non-small cell lung cancer who are resistant or intolerant to crizotinib
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/58f4ee66587b41adbd8b14a79bca7393
work_keys_str_mv	AT jainrk spotlightonbrigatinibanditspotentialinthetreatmentofpatientswithmetastaticalkpositivenonsmallcelllungcancerwhoareresistantorintoleranttocrizotinib AT chenh spotlightonbrigatinibanditspotentialinthetreatmentofpatientswithmetastaticalkpositivenonsmallcelllungcancerwhoareresistantorintoleranttocrizotinib
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Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib

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