Subsequently, more potent second-generation ALK TKIs, including ceritinib,302 alectinib,303 brigatinib,304 envonalkib305 and ensartinib,306 had been developed to overcome resistance to crizotinib and enhance central nervous system (CNS) efficacy, thereby supplanting them as the standard first-line therapy for NSCLC patients harboring ALK rearrangements (often resulting in 12-month PFS rates of approximately 65%, compared to 45%).304. Here, ALK is linked to non-small cell lung carcinoma.