Brigatinib: New-generation ALK inhibitor for nonsmall cell lung cancer

Umbela, Stewart; Ghacha, Shahinaz; Matuknauth, Revika; Gause, Stacey; Joshee, Shrijana; Deshmukh, Rahul

doi:10.1016/j.currproblcancer.2019.03.005

Cited by 6 publications

(7 citation statements)

References 16 publications

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“…Based on these data brigatinib was approved in 2017 by the FDA as second-line treatment after crizotinib failure, followed by approval for untreated ALK-positive NSCLC patients in 2019 [ 48 ]. Approvals were also granted by the EMA.…”

Section: Current Anaplastic Lymphoma Kinase (Alk) Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer

Kauffmann-Guerrero

Kahnert

Huber

2020

Drugs

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Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and is the leading cause of cancer-related deaths. Most NSCLC patients are diagnosed with advanced disease and require systemic treatment. Despite emerging advances in chemotherapy and immunotherapy, the prognosis of stage IV patients remains poor. However, the discovery of oncogenic driver mutations including mutations in the epidermal growth factor receptor (EGFR), the anaplastic lymphoma kinase (ALK) and others, characterize a subset of patients with the opportunity of targeted therapies. Fusions between the ALK and echinoderm microtubule-associated protein-like 4 (EML4) are present in ∼ 3–5% of patients with NSCLC. Several first-, second-, and third-generation ALK tyrosine kinase inhibitors (TKIs) have been developed in the last decade and have tremendously changed treatment options and outcomes of ALK-positive NSCLC patients. With increasing treatment options, treatment sequence decisions have become more and more complex. ALK-mutations, fusion variants, or activation of by-pass pathways result in treatment resistance during the course of treatment in nearly all patients. Mutation-guided treatment sequencing can lead to better outcomes, and re-biopsy or liquid-biopsy should be performed whenever possible in case of disease progression in ALK-rearranged patients. In the future, combinational treatment of ALK TKIs with other pathway-inhibitors might further improve patients’ treatment options and outcomes. Here, we review the data for currently available ALK TKIs, discuss approaches of treatment sequencing, and give an outlook on emerging developments.

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Section: Current Anaplastic Lymphoma Kinase (Alk) Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer

Kauffmann-Guerrero

Kahnert

Huber

2020

Drugs

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“…Among the mechanisms of resistance to brigatinib, gene mutations such as D1203, S1206, E1210K + S1206C, and E1210K + D1203N have been identified [ 106 ]. The molecular structure of brigatinib, which may lead to resistance development, is also influenced by the L1196M, G1269A, F1174L, and R1275Q mutations [ 107 , 108 ]. Furthermore, it has been discovered that the mutation G1202R occurs after previous exposure to ceritinib, alectinib, and brigatinib, meaning that lorlatinib is the only efficient therapeutic agent [ 108 , 109 ].…”

Section: Resultsmentioning

confidence: 99%

An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance

Pătcaș

Chiș

Militaru

et al. 2021

Bosn J of Basic Med Sci

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Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown Read more in PDF.

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“…It is effective against the EGFR C797S-T790M-del19 triple mutant ( 79 ). Brigatinib received approval for the treatment of anaplastic lymphoma kinase-positive metastatic NSCLC patients who had progressive disease while taking crizotinib or who were intolerant to crizotinib ( 80 ).…”

Section: Egfr Inhibitors Used Clinicallymentioning

confidence: 99%

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

Duan

et al. 2022

Front. Oncol.

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Epidermal growth factor receptor (EGFR) inhibitors are widely used to treat various types of cancers such as non-small cell lung cancer, head and neck cancer, breast cancer, pancreatic cancer. Adverse reactions such as skin toxicity, interstitial lung disease, hepatotoxicity, ocular toxicity, hypomagnesemia, stomatitis, and diarrhea may occur during treatment. Because the EGFR signaling pathway is important for maintaining normal physiological skin function. Adverse skin reactions occurred in up to 90% of cancer patients treated with EGFR inhibitors, including common skin toxicities (such as papulopustular exanthemas, paronychia, hair changes) and rare fatal skin toxicities (e.g., Stevens–Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis). This has led to the dose reduction or discontinuation of EGFR inhibitors in the treatment of cancer. Recently, progress has been made about research on the skin toxicity of EGFR inhibitors. Here, we summarize the mechanism of skin toxicity caused by EGFR inhibitors, measures to prevent severe fatal skin toxicity, and provide reference for medical staff how to give care and treatment after adverse skin reactions.

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Brigatinib: New-generation ALK inhibitor for nonsmall cell lung cancer

Cited by 6 publications

References 16 publications

Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer

Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer

An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

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