Alectinib in the treatment of ALK-positive non-small cell lung cancer: an update on its properties, efficacy, safety and place in therapy

Tiziana Vavalà, Silvia Novello, Tiziana Vavalà, Silvia Novello

Abstract

Anaplastic lymphoma kinase (ALK) rearrangement is identified in 3-7% of advanced non-small cell lung cancer (NSCLC) cases, and ALK tyrosine kinase inhibitors (TKIs) have revolutionized the management of this subset of NSCLC patients. ALK-TKIs have been proven highly effective in ALK-rearranged advanced NSCLC patients, but after initial responses and benefit, a subsequent progression inevitably occurs. Understanding acquired-resistance mechanisms and defining an appropriate algorithm is becoming even more essential, particularly considering the availability of extremely efficacious next-generation ALK inhibitors. The aim of this review is the analysis of current data about ALK inhibition as a therapeutic strategy in ALK-rearranged NSCLC management, with a focus on a specific ALK-TKI, alectinib. Alectinib is a highly selective inhibitor of ALK and showed systemic and central nervous system (CNS) efficacy in the treatment of this particular population. The change of first-line approach, and consequently of further lines of therapy, in ALK-rearranged NSCLC patients is still a matter of debate. A summary of evidence from randomized trials evaluating alectinib will be presented in order to discuss the available clinical evidence, safety and place in therapy.

Keywords: ALK; ALK inhibitors; ALK-rearranged NSCLC; ALK–TKI; ALK–tyrosine kinase inhibitors; EML4–ALK; NSCLC; alectinib; alectinib clinical trials; non-small cell lung cancer.

Conflict of interest statement

Conflict of interest statement: Dr Tiziana Vavalà declares no conflicts of interests. Professor Silvia Novello declares these conflicts of interests in the last 3 years: speaker bureau Eli Lilly, BMS, BI, Incyte, MSD, Roche and Astra Zeneca.

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