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First-line treatment of advanced ALK-positive non-small-cell lung cancer

Authors Gandhi S, Chen H, Zhao Y, Dy G

Received 29 May 2015

Accepted for publication 23 July 2015

Published 18 September 2015 Volume 2015:6 Pages 71—82


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Pan-Chyr Yang

Shipra Gandhi,1 Hongbin Chen,2 Yujie Zhao,2 Grace K Dy2

1Department of Internal Medicine, State University of New York, 2Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

Abstract: Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer deaths, both within the US and worldwide. There have been major treatment advances in NSCLC over the past decade with the discovery of molecular drivers of NSCLC, which has ushered in an era of personalized medicine. There are several actionable genetic aberrations in NSCLC, such as epidermal growth factor receptor and anaplastic lymphoma kinase (ALK). In 3%–7% of NSCLC, a chromosomal inversion event in chromosome 2 leads to fusion of a portion of the ALK gene with the echinoderm microtubule–associated protein-like 4 (EML4) gene. The constitutive activation of the ALK fusion oncogene renders it vulnerable to therapeutic intervention. This review focuses on the first-line treatment of advanced ALK-positive NSCLC using ALK inhibitors. Crizotinib was the first agent proven to be efficacious as first-line treatment for ALK-positive NSCLC. However, acquired resistance inevitably develops. The central nervous system is a sanctuary site that represents a common site for disease progression as well. Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood–brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well. In this review, we provide summary of the clinical experience with these drugs in the treatment of ALK-positive NSCLC.

Keywords: non-small-cell lung cancer, ALK, first line, crizotinib, pemetrexed

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