...patients with EGFRm NSCLC that developed T790m resistance on 1st/2nd generation EGFR TKI were treated with osimertinib. At baseline and every 8 weeks, patients were radiologically evaluated with CT and blood was drawn for next generation sequencing of circulating tumor DNA (ctDNA) using the Avenio ctDNA expanded panel. Patients were treated with osimertinib until radiological progression (RECISTv1.1). The aim of this study was to identify % of patients in which resistance could be detected using ctDNA analysis prior to progressive disease (PD). The primary EGFR driver was detected in 19/23 (83%) and in 17/23 (74%) EGFR T790M was found. Co-alterations leading possibly to osimertinib resistance were detected in 11/19 (58%) patients prior to PD (BRAFV600E 2; ERBB2m 1; METm 2; EGFRC797Sm 2; PIK3CAm 1; ERBB2amp 2; METamp 7). Detection of the oncogenic driver and monitoring evolution of resistance prior to PD is possible in a selected group of patients with detectable ctDNA at the start of osimertinib treatment.