Abstract
Anaplastic lymphoma kinase (ALK) mutations were first described in non-small cell lung cancer (NSCLC) in 2007. ALK inhibitors are anti-cancer drugs that act on tumours with variations of ALK such as an EML4-ALK translocation.
ALK inhibitors have shown significant benefits in the management of ALK-positive NSCLC compared to conventional chemotherapy. Crizotinib was the first ALK inhibitor which compared to standard chemotherapy prolonged progression-free survival.
However, many patients with ALK-positive experience clinical progression and frequent brain metastases in the first year of treatment with crizotinib during the poor accumulation of the drug in the central nervous system (CNS). Second-generation (alectinib, ceritinib, brigatinib) and the third-generation ALK inhibitors (lorlatinib), have increased potency and higher CNS activity compared to the first-generation crizotinib.
A sequencing of ALK inhibitors in ALK-positive NSCLC prolonged an overall survival