Brigatinib and the new generation of ALK-inhibitors for non-small cell lung cancer

About 2–7% of non-small cell lung cancer (NSCLC) is driven by the fusion protein between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) (1). The first ALK-inhibitor approved for the treatment of NSCLC was crizotinib with an objective response rate (ORR) up to 74%. Despite this, progression-free survival (PFS) on crizotinib is only 10.9 months, and the cancer invariably recurs with 25–50% of recurrences in the CNS (1,2) (Table 1). Given the protracted natural history of metastatic ALK-rearranged NSCLC in the CNS, treatment options aside from those causing significant neurocognitive degeneration, such as whole brain radiotherapy, are limited (10).