PURPOSE OF REVIEW: The review will highlight recent advances in development of 
ALK-TKIs and management of patients with ALK-positive nonsmall cell lung cancer.
RECENT FINDINGS: There has been rapid progress in the use of targeted therapies 
for ALK-positive NSCLC. Since the discovery, development and approval of 
crizotinib in 2011, three second-generation ALK-TKIs, ceritinib, alectinib and 
brigatinib have been approved by the FDA. A range of newer generation ALK 
inhibitors with improved potency against ALK and against mutations that confer 
resistance to crizotinib are in clinical development.
SUMMARY: Our review will discuss the recent phase III data with ceritinib and 
alectinib as well as clinical trials with other ALK inhibitors. We will also 
address two important issues in the management of ALK-positive NSCLC, prevention 
and treatment of brain metastases and management of emergent ALK-TKI resistance 
mechanisms.