Osimertinib Treatment on EGFR T790M Plasma Positive NSCLC Patients (APPLE)

Inclusion: Registration: * Pathological diagnosis of adenocarcinoma of the lung carrying common EGFR activating mutations associated with EGFR-TKI sensitivity (Del19 or L858R); performed locally; no other EGFR mutations will be allowed. In case of other (than EGFR) concomitant mutations, discussion with EORTC Headquarters is mandatory; * Stage IV NSCLC; * Blood sample available for cfDNA EGFR T790M central testing; * Age ≥18 years; * EGFR TKI treatment-naïve eligible to receive first-line treatment with EGFR TKI; * Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) if performed more than 12 months before registration; * Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations Randomization: * Report of adequacy sample for cfDNA EGFR T790M test by central laboratory; * Prior palliative radiotherapy or surgery are allowed if completed at least 4 weeks before the randomization; * Patients with brain metastases are allowed provided they are stable (i.e. without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and without deterioration of any neurologic symptoms), and have not received steroids for at least 7 days before randomization; Baseline tumor assessment scans are done within 21 days before randomization; * Evaluable disease as defined below; * At least one lesion, not previously irradiat…