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New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib

Authors Rothschild SI

Received 12 March 2016

Accepted for publication 31 March 2016

Published 5 May 2016 Volume 2016:12 Pages 735—741

DOI https://doi.org/10.2147/TCRM.S87876

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Garry Walsh

Sacha I Rothschild

Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland

Abstract: Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%–8% of non-small-cell lung cancer (NSCLC) patients. Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial. Despite the initial treatment response of crizotinib, disease progression inevitably develops after approximately 10 months of therapy. Different resistance mechanisms have recently been described. One relevant mechanism of resistance is the development of mutations in ALK. Novel ALK tyrosine kinase inhibitors have been developed to overcome these mutations. Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naïve ALK-positive disease. In this paper, preclinical and clinical data of ceritinib are reviewed, and its role in the clinical setting is put into perspective.

Keywords: lung cancer, ALK, ceritinib, crizotinib

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