With that said, although ceritinib and entrectinib are less effective towards crizotinib-resistant malignancies, they showed increased efficacy towards brain metastasis with entrectinib the current preferred and FDA-approved first-line treatment for those with metastatic brain involvement [46] According to the latest results from various clinical trials, repotrectinib and lorlatinib are the most potent ROS1 inhibitors, with good CNS activity and the ability to overcome resistance resulting from bypass signalling activation and alternative ROS1 mutations. The gene discussed is ROS1; the disease is metastasis.