Neurocognition in NSCLC Patients Treated With Osimertinib or Osimertinib + WBI

Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures 2. Male or female, aged at least 18 years 3. Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1 4. Life expectancy of at least 3 months 5. Histologically or cytologically documented metastatic NSCLC, which are not amenable to curative surgery or radiotherapy, patients must be classified as stage IIIB-IV. Staging will be according to the TNM staging system for lung cancer (8th edition) 6. Histologically documented that with sensitizing EGFR mutations(either L858R or Exon19del) 7. symptomatic brain metastasis, with at least three metastatic lesions in the brain which need WBI based on investigator's decision. Symptom score 1-6 point.(notes: Symptomatic definition: Symptoms without acute intervention or hospitalization, symptoms including but not limited in headache, nausea, dizziness, and sensory disturbance, but without hospitalization or medical emergency.) 8. HVLT-R score 15 point (Notes: this number is based on the data in a study in Chinese population) 9. At least 1 measurable lesion in the brain according to RECIST 1.1; At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter with computed tomography (CT) or magnetic resonance imaging (MRI). 10. No previous treatment with EGFR-TKI or other systemic treatment, as well as radiotherapy for brain metastases. 11. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential, or must have 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 considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution * Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation Further information in Appendix E(Definition of Women of Childbearing Potential and Acceptable Contraceptive Methods) 12. Male subjects should be willing to agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined below: a. With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last dose of Osimertinib. b. Men must refrain from donating sperm during this same period Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) 2. Previous randomisation in the present study or previous treatment with osimertinib 3. Leptomeningeal met alone or synchronously is not allowed 4. History of hypersensitivity to active or inactive excipients of Osimertinib or drugs with similar chemical structure or class to Osimertinib 5. For patients, inability to collect plasma, CSF and tissue at baseline 6. 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). Screening for chronic conditions is not required. 7. Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 week prior) (Appendix D). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. 8. 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. 9. Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value (Note: patients with congenital long QT syndrome (CLQTS) are excluded from this study.) * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. * Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium \< LLN; Serum/plasma magnesium \< LLN; Serum/plasma calcium \< LLN) , 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 and cause Torsades de Pointes 10. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. 11. Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values: * Absolute neutrophil count \<1.5 x 109/L; * Platelet count \<100 x 109/L; * Haemoglobin \<90 g/L; * Alanine aminotransferase \>2.5 x ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases; * Aspartate aminotransferase \>2.5 x ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases; * Total bilirubin \>1.5 x ULN if no liver metastases or \>3 x ULN in the presence of documented Gilbert's Syndrome \[unconjugated hyperbilirubinaemia\] or liver metastases; * Serum creatinine \>1.5 x ULN concurrent with creatinine clearance \<50 mL/min \[measured or calculated by Cockcroft and Gault equation\] 12. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. 13. Women who are pregnant or breast-feeding.