4.5 Review

Safety and efficacy of anaplastic lymphoma kinase tyrosine kinase inhibitors in non-small cell lung cancer

Journal

ONCOLOGY REPORTS
Volume 45, Issue 1, Pages 13-28

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/or.2020.7851

Keywords

anaplastic lymphoma kinase tyrosine kinase inhibitors; crizotinib; ceritinib; brigatinib; alectinib; lorlatinib; entrectinib; safety; non-small cell; efficacy

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ALK-TKIs have shown excellent clinical efficacy in treating ALK-positive NSCLC as first-line therapy, but resistance and adverse effects remain challenges. Proper management of these adverse effects is crucial in improving patient quality of life.
Since the discovery of targeted therapy with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have been introduced as the first-line treatment for non-small cell lung cancer (NSCLC) patients who carry sensitizing ALK-activating mutations. Compared with conventional chemotherapeutic regimens, small-molecule ALK-TKIs exhibit excellent clinical efficacy in ALK-positive NSCLC. A series of studies have indicated that ALK-TKI agents as the first-line treatment, including crizotinib, ceritinib, brigatinib, alectinib and entrectinib, can benefit patients with ALK-positive NSCLC. However, resistance to ALK-TKIs has emerged. ALK-TKIs are associated with significantly disabling and undesirable effects that adversely impact quality of life and compliance. This study reviews the pharmacodynamics, efficacy and safety of ALK-TKI agents in order to summarize these effects as well as the relevant management strategies. It is worth emphasizing that the frequency and severity of an adverse effect often varies across different trials.

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