ALK and non-small cell lung carcinoma: Moreover, brigatinib was granted accelerated approval by the FDA in 2017 as second-line therapy for patients with ALK-positive metastatic NSCLC, based on the considerable systemic and intracranial responses in clinical trials.26 Similar to the experience with crizotinib, novel resistance mechanisms were observed in patients who relapsed after treatment with second-generation ALK inhibitors.