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 irradiated and not chosen for biopsy during the
             study screening period, that can be accurately measured at baseline as ≥10 mm in the
             longest diameter (except lymph nodes which must have a short axis of ≥15 mm) with
             computed tomography (CT) or magnetic resonance imaging (MRI), and which is suitable
             for accurate repeated measurements.

          -  WHO Performance Status 0-2, with no clinically significant deterioration over the
             previous 2 weeks and a minimum life expectancy of 12 weeks;

          -  Adequate bone marrow, renal, hepatic and liver function within 21 days from
             randomization and defined as follows:

          -  Absolute neutrophil count ≥1.5 x 109/L;

          -  Platelet count ≥100 x 109/L;

          -  Haemoglobin ≥9 g/dL;

          -  Alanine aminotransferase (ALT) ≤2.5x the upper limit of normal (ULN) if no
             demonstrable liver metastases or ≤5xULN in the presence of liver metastases;

          -  Aspartate aminotransferase (AST) ≤2.5xULN if no demonstrable liver metastases or
             ≤5xULN in the presence of liver metastases;

          -  Total bilirubin ≤1.5xULN if no liver metastases or ≤3xULN in the presence of
             documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases;

          -  Serum creatinine ≤1.5xULN concurrent with creatinine clearance ≥50 mL/min (measured or
             calculated by Cockcroft and Gault equation);

          -  No significant comorbidity that according to the investigator would hamper the
             participation on the trial;

          -  Female patients should be using adequate contraceptive measures, should not be
             breastfeeding, until 12 months after the last dose, and must have a negative pregnancy
             test (serum or urine) prior to first dose of study drug (within 72 hours); or female
             patients must have an evidence of non-child-bearing potential by fulfilling one of the
             following criteria at screening:

          -  Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12
             months following cessation of all exogenous hormonal treatments.

          -  Women under 50 years old would be consider postmenopausal if they have been
             amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
             and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the
             post-menopausal range for the institution.

          -  Documentation of irreversible surgical sterilisation by hysterectomy,
             bilateraloophorectomy, or bilateral salpingectomy but not tubal ligation.

          -  Male patients should be willing to use barrier contraception, i.e., condoms

             o Male patients will be advised to arrange for the freezing of sperm samples prior to
             the start of the study should they wish to father children, and not to donate sperm
             until 6 months after discontinuation of study treatment." (as per Investigator
             Brochure, IB)

          -  Absence of any psychological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule; those
             conditions should be discussed with the patient before registration in the trial.

        Exclusion:

          -  Treatment with any of the following:

          -  Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic
             NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational
             drug;

          -  Prior treatment with an EGFR-TKI;

          -  Major surgery (excluding placement of vascular access) within 4 weeks before
             randomization;

          -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
             radiation within 4 weeks before randomization

          -  Patients currently receiving (or unable to stop use at least 1 week prior to receiving
             the first dose of study drug) medications or herbal supplements known to be potent
             inhibitors or inducers of cytochrome P450 (CYP) 3A4;

          -  Other anti-cancer therapies and alternative medications such as homeopathic treatment,
             etc;

          -  Treatment with an investigational drug within five half-lives of the compound or any
             of its related material, if known;

          -  Leptomeningeal carcinomatosis; spinal cord compression;

          -  Any unresolved toxicities from prior systemic therapy (e.g., adjuvant chemotherapy)
             greater than CTCAE grade 2 at the time of randomization;

          -  Patients will not be eligible if they have evidence of active malignancy (other than
             non-melanoma skin cancer or localized cervical cancer or localised and presumed cured
             prostatic cancer) within 2 years before randomization and are not receiving specific
             treatment for these malignancies at baseline assessment;

          -  Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension and active bleeding diatheses, which in the Investigator's opinion makes
             it undesirable for the patient to participate in the trial or which would jeopardise
             compliance with the protocol; or active infection including hepatitis B, hepatitis C
             and human immunodeficiency virus (HIV). Active infection will include any patients
             receiving intravenous treatment for infection; active hepatitis B infection will, at a
             minimum, include all patients who are Hepatitis B surface antigen positive (HbsAg
             positive) based on serology assessment. Screening for chronic conditions is not
             required;

          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
             swallow the formulated product, or previous significant bowel resection that would
             preclude adequate absorption of Osimertinib or Gefitinib;

          -  Any of the following cardiac criteria:

          -  Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs using local
             clinic ECG machine-derived QTcF value

          -  Any clinically important abnormalities in rhythm, conduction, or morphology of resting
             ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree
             heart block, PR interval >250 msec or history of episodes of bradycardia (<50 BPM);

          -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
             such as heart failure, hypokalaemia, congenital long QT syndrome family history of
             long QT syndrome, or unexplained sudden death under 40 years of age in first-degree
             relatives or any concomitant medication known to prolong the QT interval.

          -  Abnormal cardiac function: LVEF < 50% (assessed by MUGA or ECHO)

          -  Past medical history of ILD (Interstitial Lung Disease), drug-induced ILD, radiation
             pneumonitis which required steroid treatment, or any evidence of clinically active
             ILD.