RET and lung carcinoma: Using a highly active agent in the CNS is crucial in RET fusion-positive lung cancers, because close to 25% of patients present with intracranial disease at baseline, whereas the lifetime prevalence of brain metastases approaches 50%.14 In addition, LOXO-292 was designed to target potential resistance mechanisms that can emerge from prior multikinase inhibitor use, such as RET V804M/L gatekeeper substitutions.