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Clin Lung Cancer. 2015 Mar;16(2):86-91. doi: 10.1016/j.cllc.2014.09.011. Epub 2014 Oct 13.

Ceritinib (LDK378): a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer.

Author information

1
Department of Spine Surgery, the Affiliated Hospital of Luzhou Medical College, Luzhou, China. Electronic address: senlimd@126.com.
2
Department of Gastroenterology, Tongji Hospital, Tongji Unversity School of Medicine, Shanghai, China.
3
Department of Oncology, Jingjiang People's Hospital, Jingjiang, China.
4
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

The success in identifying the chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) as an oncogenic driver has thoroughly changed the treatment of non-small-cell lung cancer. In the past decade, targeted drugs have emerged as an efficient personalized strategy for ALK-rearranged non-small-cell lung cancer. The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.

KEYWORDS:

ALK inhibitor; Clinical trial; Cost-effectiveness; Pharmacokinetics; Resistance

PMID:
25458559
DOI:
10.1016/j.cllc.2014.09.011
[Indexed for MEDLINE]

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