Safety and Tolerability of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer

Danilo Rocco, Ciro Battiloro, Luigi Della Gravara and Cesare Gridelli ()
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Danilo Rocco: Azienda Ospedaliera Dei Colli Monaldi
Ciro Battiloro: Azienda Ospedaliera Dei Colli Monaldi
Luigi Della Gravara: “Luigi Vanvitelli” University
Cesare Gridelli: “S.G. Moscati” Hospital

Drug Safety, 2019, vol. 42, issue 2, No 4, 199-209

Abstract: Abstract The chimeric protein echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, resulting from the rearrangement of the homonym genes, is one of the currently targetable oncogenic drivers in anaplastic lymphoma kinase-positive non-small-cell lung cancer. In fact, four first- and second-generation anaplastic lymphoma kinase tyrosine kinase inhibitors, crizotinib (PF-02341066), ceritinib (LDK378), alectinib (CH5424802), and brigatinib (AP26113), are presently approved for clinical practice; however, these agents are not devoid of complications and thus should be administered meaningfully. Furthermore, third-generation inhibitors are currently under development to overcome acquired resistance mechanisms inevitably resulting from treatment with first- and second-generation tyrosine kinase inhibitors. Therefore, this article aims to provide a comprehensive state-of-the-art review about the pharmacodynamics, pharmacokinetics, safety, and tolerability profiles of currently available and promising under-development anaplastic lymphoma kinase tyrosine kinase inhibitors.

Date: 2019
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DOI: 10.1007/s40264-018-0771-y

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