The Study: This exploratory analysis of two early phase trials of brigatinib takes a look specifically at the sizeable chunk of enrolled patients who had brain metastases. First things first, brigatinib is a next generation ALK-targeted tyrosine kinase inhibitor. Remember, crizotinib is the first-generation treatment for ALK-rearranged NSCLC, but it isn’t super active in the brain. Alectinib, on the other hand, is pretty active with an observed 11-month duration of intracranial disease control. The bulk of the new brigatinib data comes from the phase 2 ALTA trial that randomized patients who failed crizotinib to two different doses of brigatinib. Over two-thirds of enrollees had brain mets, though little more than half of these had previous brain radiation. Importantly, exclusion criteria included any symptoms from brain mets and/or ECOG >2. The higher dose (180 mg daily) of brigatinib had a nearly 70% intracranial response rate with a 18-month median duration and a 60% systemic response rate with a 12-month median duration, which is all favorable compared to alectinib. That’s great, but it remains unclear how the role of radiation in managing brain metastases is incorporated (understood?) by those designing large randomized novel drug trials.
Bottom Line: Among the majority of patients with ALK-rearranged NSCLC who progress in the brain after crizotinib, brigatinib has a 70% intracranial response rate lasting up to 18 months. | Camidge, J Clin Oncol 2018