Article Abstract

Alectinib can replace crizotinib as standard first-line therapy for ALK-positive lung cancer

Authors: Takehiro Uemura, Toyoaki Hida


In 2007, Soda and colleagues identified anaplastic lymphoma kinase (ALK) rearrangement in adenocarcinoma of the lung (1). Approximately 5% of non-small cell lung cancer (NSCLC) cases have ALK rearrangement and the incidence of ALK-positive NSCLC is similar across all regions of the world. For patients with ALK-positive NSCLC, crizotinib (Xalkori; Pfizer), which is an ALK-targeted tyrosine kinase inhibitor (TKI), had been the standard first-line therapy that enabled patients to achieve prolonged progression-free survival (PFS) (2-5). However, treatment of ALK-positive NSCLC with crizotinib has some problems. First, most patients relapse within a year of treatment due to a variety of resistance mechanisms. Second, crizotinib is generally well tolerated; however, a number of significant toxicities, like gastrointestinal side effects, may occur sometimes and require dose modification or treatment discontinuation (4,5). Third, crizotinib has poor penetration to the central nervous system (CNS), which is a common site for metastasis in ALK-positive NSCLC patients (6-8). Therefore, there has been a need for new and improved alternative agents to crizotinib.