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

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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.

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Authors and Affiliations

  1. Division of Pulmonary Oncology, Azienda Ospedaliera Dei Colli Monaldi, Naples, Italy

    Danilo Rocco & Ciro Battiloro

  2. “Luigi Vanvitelli” University, Caserta, Italy

    Luigi Della Gravara

  3. Division of Medical Oncology, “S.G. Moscati” Hospital, Contrada Amoretta, 83100, Avellino, Italy

    Cesare Gridelli

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  1. Danilo Rocco
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  2. Ciro Battiloro
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Correspondence to Cesare Gridelli.

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No sources of funding were received for the preparation of this article.

Conflict of interest

Cesare Gridelli received honoraria as a speaker bureau and advisory board member and a consultant for Pfizer, Novartis, and Roche. Danilo Rocco, Ciro Battiloro, and Luigi Della Gravara have no conflicts of interest that are directly relevant to the contents of this article.

Additional information

Part of a theme issue on “Safety of Novel Anticancer Therapies: Future Perspectives”. Guest Editors: Rashmi R. Shah, Giuseppe Curigliano.

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Rocco, D., Battiloro, C., Della Gravara, L. et al. Safety and Tolerability of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer. Drug Saf 42, 199–209 (2019). https://doi.org/10.1007/s40264-018-0771-y

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