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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

Authors Jain RK, Chen H

Received 4 August 2017

Accepted for publication 13 September 2017

Published 13 October 2017 Volume 2017:8 Pages 169—177

DOI https://doi.org/10.2147/LCTT.S126507

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Sai-Hong Ignatius Ou


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

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