| Reference | 1. Lung Cancer (Auckl). 2017 Oct 13;8:169-177. doi: 10.2147/LCTT.S126507.
eCollection 2017. <br />
<br />
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. <br />
<br />
Jain RK(1), Chen H(1). <br />
Author information: <br />
(1)Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA. <br />
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. <br />
<br />
2. Drugs Today (Barc). 2017 Aug;53(8):435-446. doi: 10.1358/dot.2017.53.8.2676119. <br />
<br />
Brigatinib for the treatment of ALK-positive advanced non-small cell lung cancer
patients. <br />
<br />
Passaro A(1), Prelaj A(2), Pochesci A(3), Spitaleri G(3), Rossi G(3), Del Signore
E(3), Catania C(3), de Marinis F(3). <br />
Author information: <br />
(1)Division of Thoracic Oncology, European Institute of Oncology (IEO), Milan,
Italy. [email protected].
(2)Division of Thoracic Oncology, European Institute of Oncology (IEO), Milan,
Italy and Department of Medical Oncology, Policlinico Umberto I, /Sapienza/
University of Rome, Rome, Italy.
(3)Division of Thoracic Oncology, European Institute of Oncology (IEO), Milan,
Italy. <br />
Brigatinib (AP-26113, Alunbrig) is a second-generation anaplastic lymphoma kinase
(ALK) tyrosine kinase inhibitor (TKI) that is highly active in non-small cell
lung cancer (NSCLC) harboring ALK translocation. Brigatinib was found to be very
active against different ALK resistance mutations that mediate acquired
resistance biology processes, particularly G1269A ALK C1156Y, I1171S/T, V1180L
and others. Different clinical trials evaluated the activity of brigatinib in
crizotinib-resistant patients, confirming high activity with durable response not
only in parenchymal disease, but also in intracranial disease. Nowadays,
brigatinib is under evaluation in different clinical trials exploring TKI-naive
patients in the first-line setting. On the basis of its significant activity
results, brigatinib received approval by the FDA for the treatment of patients
with ALK-positive metastatic NSCLC who have progressed on or are intolerant to
crizotinib. <br />
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