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Lorlatinib for the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer.

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Published:1st Mar 2019
Author: Yang J, Gong W.
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Ref.:Expert Rev Clin Pharmacol. 2019;12(3):173-178.
DOI:10.1080/17512433.2019.1570846
Lorlatinib for the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer


Introduction:
Approximately 3–5% of patients with non-small cell lung cancer (NSCLC) belonged to anaplastic lymphoma kinase (ALK)-positive NSCLC. The treatment drugs of ALK-positive NSCLC mainly included crizotinib, ceritinib, alectinib, and brigatinib. Although these drugs had some effects, most of them were usually easy to develop drug resistance. Lorlatinib is a new inhibitor of ALK for treating ALK-positive NSCLC,the effect is obvious, and not easy to develop resistance.

Areas covered: The main mechanism of action, pharmacokinetics, clinical efficacy and safety of lorlatinib were introduced in this paper.

Expert commentary: Lorlatinib is a new, reversible, ATP-competitive small molecule inhibitor of ALK and c-ros oncogene 1 (ROS1). It can inhibit tumor cell growth in ALK- and ROS1-overexpressing tumor cells. Clinical trial indicated that lorlatinib had obvious therapeutic effect for patients with ALK-positive NSCLC. Lorlatinib could also pass through the blood-brain barrier, which had a good effect on patients with brain metastasis. Adverse events of lorlatinib were mostly mild and moderate in severity, and patients were easily tolerated. Most common adverse events were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.


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