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Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors

Authors Singh A, Chen H

Received 28 April 2020

Accepted for publication 9 July 2020

Published 30 July 2020 Volume 2020:12 Pages 6615—6628


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly

Abhay Singh, Hongbin Chen

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

Correspondence: Hongbin Chen
Department of Medicine, Roswell Park Comprehensive Cancer Center, Elm and Carlton Street, Buffalo, NY 14263, USA
Tel +1 716 845 3099
Fax +1 716 845 8935

Abstract: The treatment of advanced non–small-cell lung cancer (NSCLC) has undergone a paradigm shift in the last decade. Molecular characterization of the disease has led to the rapid development of personalized medicine and swift delivery of targeted therapies to patients. The discovery of the anaplastic lymphoma kinase (ALK) gene in patients with NSCLC has resulted in rapid bench–bedside transition of several active drugs, with several others currently in clinical trials. After the first-generation ALK inhibitor crizotinib, next-generation ALK inhibitors have entered clinical applications for ALK-rearranged NSCLC. Ceritinib, alectinib, and brigatinib have all received approval for ALK-positive patients who have failed prior crizotinib, as well as first-line therapy in treatment-naïve patients based on favorable efficacy. Most recently, lorlatinib, a potent, newer-generation ALK inhibitor, has been approved as second- or third-line treatment. These advances have led to better patient outcomes, but concurrently have led to several crucial unanswered questions about optimal care for ALK-positive NSCLC patients. The ultimate acquisition of resistance to ALK-inhibitor therapy poses a challenge to ongoing research efforts, in addition to the routine management of these patients in the clinic. This review provides a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlights current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC.

Keywords: non–small cell lung cancer, ALK rearrangement, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib

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