The ongoing phase II APPLE trial (NCT02856893) assesses the optimal strategy for delivering osimertinib in EGFR-mutant NSCLC patients and will prospectively validate the efficacy of osimertinib among those patients with BM at baseline (stratification criteria and brain MRI will be performed at baseline) and also the time to radiological brain progression respect to with first-generation EGFR TKI (gefitinib) (140). This evidence concerns the gene EGFR and non-small cell lung carcinoma.