Drug Safety

, Volume 42, Issue 2, pp 199–209 | Cite as

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

  • Danilo Rocco
  • Ciro Battiloro
  • Luigi Della Gravara
  • Cesare GridelliEmail author
Review Article


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.


Compliance with Ethical Standards


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.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Danilo Rocco
    • 1
  • Ciro Battiloro
    • 1
  • Luigi Della Gravara
    • 2
  • Cesare Gridelli
    • 3
    Email author
  1. 1.Division of Pulmonary OncologyAzienda Ospedaliera Dei Colli MonaldiNaplesItaly
  2. 2.“Luigi Vanvitelli” UniversityCasertaItaly
  3. 3.Division of Medical Oncology“S.G. Moscati” HospitalAvellinoItaly

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