The treatment framework for advanced non-small-cell lung cancer harbouring anaplastic lymphoma kinase (ALK) fusions has changed substantially since the discovery of crizotinib, a first-generation ALK tyrosine-kinase inhibitor (TKI). Three generations of ALK TKIs have since been developed, with increasing potency, CNS penetrance, and ability to overcome ALK-resistance mutations with each successive generation.1 Multiple phase 3 trials have shown superior efficacy of second-generation ALK TKIs (alectinib, brigatinib, and ensartinib) compared with crizotinib, establishing next-generation ALK TKIs as preferred initial therapy.