A phase II trial on efficacy and safety of osimertinib in elderly EGFR T790M-positive non-small-cell lung cancer patients who progressed during prior EGFR-TKI treatment or had recurrence (SPIRAL Study)
1. Patients with stage IIIB/IV whose stage was histologically or cytologically confirmed as non-small-cell lung cancer and post-operative recurrence
2. Patients with recurrence after the effect of higher than SD was observed or not effective (less than stable disease (SD) in best overall response according to RECIST) by treatment of EGFR-TKI (e.g.: such as erlotinib, gefitinib, afatinib) for non-small-cell lung cancer
3. NSCLC harbouring EGFR (activating) mutation and T790M positive
4. Patients capable of treatment with oral medicine
5. Patients have at least one measurable lesion according to RECIST criteria
6. Performance Status(ECOG) 0-1
7. In principle, Patients capable of participating this study under at least 2 weeks admission to the hospital or corresponding management
8. Patients are >=75 years of age (age at the time of enrollment).
9. Patients for whom bone marrow, hepatic, and renal functions have all been confirmed as normal within 14 days prior to enrollment according to the following clinical test standards:
1) WBC >= 3,000/mm3 - <= 12,000/mm3
2) Neutrophil count>=1,500/mm3
3) Platelet count >= 100,000/mm3
4) Haemoglobin >= 9.0g/dL
5) AST, ALT <= 100 IU/L
6) Total bilirubin <= 1.5mg/dL
7) Creatinine <= 2.0mg/dL
8) SpO2 (Room air) >= 90%
10. Patients with life expectancy of at least 3 months
11. Patients whose following period after prior treatment passed in the planned starting point of administration (eligible from the same day after passed period)
1) Chemotherapy: passed >= 4weeks after the final treatment of prior chemotherapy
2) EGFR-TKI: the next day after the last administration
3) Radiation therapy in the case of chest: passed >= 12 weeks after the day of final radiation
4) In the case of radiation to other than chest: passed >= 2 weeks after the day of final radiation
5) Operation/treatment (including chest drainage) : passed >= 4 weeks after the day of final operation/treatment
12. Patients providing the written informed consent
1. Patients who have treatment history of osimertinib and other 3rd generation EGFR-TKI.
2. Patients with pulmonary disorders such as Idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, active radiation pneumonitis and drug-induced pneumonia.
3. Patients with infectious disorder need for intravenous injection of antibacterial drug and antimycotics.
4. Patients unable to swallow oral medications.
5. Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent CYP3A4 inhibitors (at least 1 week prior) and potent CYP3A4 inducer (at least 3 week prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
6. Patients under treatment or with treatment history of immune checkpoint inhibitor
7. Patients with any of the following cardiac criteria:
1) Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec
2) 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)
3) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, 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
8. Patients who are pregnant, nursing or possibly pregnant.
9. Patients with brain metastasis accompanying symptoms.
10. Patients with active double cancer.
11. Patients with uncontrollable diabetes mellitus.
12. Patients who have complications to be clinical problem
(Such as uncontrollable cardiac disease, severe cardiac arrhythmia to need medical treatment, sustained serious diarrhoea)
13. Any other patients who are regarded as unsuitable for this study by the investigators.
The primary endpoint of the overall response rate was 58.3% (95% confidence interval: 42.2%-72.9%). Because the lower limit of the confidence interval was greater than 35% of the threshold, the overall response rate was considered statistically significant and achieved the primary objective.