['locally advanced or metastatic egfr sensitising mutation positive non small cell lung cancer']
['azd9291 80 mg/40 mg + placebo', 'placebo erlotinib 150/100mg', 'placebo gefitinib 250 mg', 'erlotinib 150/100 mg', 'gefitinib 250 mg', 'placebo azd9291 80 mg/ 40 mg']

        Inclusion Criteria:

          1. Male or female, aged at least 18 years.

          2. Pathologically confirmed adenocarcinoma of the lung.

          3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or
             radiotherapy.

          4. The tumour harbours one of the 2 common EGFR mutations known to be associated with
             EGFR-TKI sensitivity (Ex19del, L858R).

          5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity
             sufficient to allow for central analysis of EGFR mutation status.

          6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible
             to receive first-line treatment with gefitinib or erlotinib as selected by the
             participating centre. Prior adjuvant and neo-adjuvant therapy is
             permitted(chemotherapy, radiotherapy, investigational agents).

          7. Provision of informed consent prior to any study specific procedures, sampling, and
             analysis.

          8. World Health Organization Performance Status of 0 to 1 with no clinically significant
             deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks

        Exclusion Criteria:

          1. Treatment with any of the following:

               -  Prior treatment with any systemic anti-cancer therapy for locally
                  advanced/metastatic NSCLC.

               -  Prior treatment with an EGFR-TKI.

               -  Major surgery within 4 weeks of the first dose of study drug.

               -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field
                  of radiation within 4 weeks of the first dose of study drug.

               -  Patients currently receiving medications or herbal supplements known to be potent
                  inducers of cytochrome P450 (CYP) 3A4.

               -  Alternative anti-cancer treatment

               -  Treatment with an investigational drug within five half-lives of the compound or
                  any of its related material.

          2. Any concurrent and/or other active malignancy that has required treatment within 2
             years of first dose of study drug.

          3. Spinal cord compression, symptomatic and unstable brain metastases, except for those
             patients who have completed definitive therapy, are not on steroids, have a stable
             neurologic status for at least 2 weeks after completion of the definitive therapy and
             steroids.

          4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension and active bleeding diatheses; or active infection including hepatitis B,
             hepatitis C and human immunodeficiency virus (HIV).

          5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
             swallow the formulated product, or previous significant bowel resection that would
             preclude adequate absorption of AZD9291.

          6. Any of the following cardiac criteria:

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

               -  Any clinically important abnormalities in rhythm, conduction, or morphology of
                  resting ECG.

               -  Any patient with any factors that increase the risk of QTc prolongation or risk
                  of arrhythmic events or unexplained sudden death under 40 years of age in
                  first-degree relatives or any concomitant medication known to prolong the QT
                  interval.

          7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
             steroid treatment, or any evidence of clinically active ILD.

          8. Involvement in the planning and/or conduct of the study
      