Unfortunately, eventually all the cases administered crizotinib would develop acquired resistance, generally within 1–2 years after the initiation of treatment.11 Second-generation (ceritinib, alectinib, brigatinib, and ensartinib) and third-generation (lorlatinib) ALK inhibitors were designed to overcome resistance to crizotinib and improve the management of CNS metastases, showing anti-tumor activity in crizotinib-refractory patients. This evidence concerns the gene ALK and neoplasm.