Alectinib—a new chapter in the management of ALK-positive lung cancer

Discovered in lung cancer in 2007, anaplastic lymphoma kinase (ALK) rearrangements have emerged as important therapeutic targets in non-small cell lung cancer (NSCLC) (1). Like epidermal growth factor receptor (EGFR) mutations, ALK rearrangements define a distinct molecular subset of NSCLC and confer sensitivity to treatment with genotype-specific tyrosine kinase inhibitors (TKIs) (2). The first ALK inhibitor to enter the clinic was crizotinib (3). In randomized phase III trials, crizotinib produced significant improvements in objective response rates (ORRs) and progression-free survival (PFS) compared to first- and second-line cytotoxic chemotherapy (4,5). This has established crizotinib as a standard of care for the management of ALK-positive NSCLC. Nonetheless, patients almost invariably relapse on crizotinib—commonly within one year.