Alectinib in untreated anaplastic lymphoma kinase-positive nonsmall cell lung cancer
Anaplastic lymphoma kinase (ALK) translocations are a validated molecular target in non-small cell lung cancer (NSCLC). ALK translocations result in the expression of a chimeric protein, exhibiting a constitutive ALK kinase activation, involved in cell proliferation, invasion and loss of apoptosis (1). ALK translocations are found in 4–7% of NSCLC, particularly in adenocarcinomas and in non-smokers (1). According to FDA and EMEA, standard first-line therapy for advanced ALK translocated NSCLC is crizotinib, a multi-target MET, ALK and ROS1 inhibitor (1,2). The use of second generation ALK inhibitors, such as ceritinib or alectinib, was initially validated at progression (3-5). More recently, these second generation ALK inhibitors were evaluated in first-line treatment. This year, ceritinib received FDA and EMEA approval in the first-line treatment for advanced ALK translocated NSCLC after the results of a phase III trial comparing ceritinib to platinum - pemetrexed chemotherapy with a benefit on progression-free survival of 16.6 vs. 8.1 months (6). Several clinical trials are underway comparing head to head different ALK inhibitors in phase III trials in ALK naive patients, as brigatinib vs. crizotinib (NCT02737501) or lorlatinib vs. crizotinib (NCT03052608).