In this study, an attempt was made to try to understand the mechanisms of resistance to osimertinib in patients with disease progression, investigating circulating tumor DNA: 50% of these patients had no-detectable ctDNA and in the remaining patients the molecular mechanisms of tumor resistance were heterogeneous (MET amplification, EGFR and KRAS amplification, MEK1, KRAS or PI3KC mutations, EGFR C797S mutations, JAK2 mutations, HER2 exon 20 mutation); importantly, there was no evidence of acquired EGFR T790M mutation in progressing patients treated with osimertinib [331]. This evidence concerns the gene KRAS and neoplasm.