Uncommon EGFR AZD9291

This is a single-arm phase II trial to evaluate the efficacy of AZD9291 (experimental) NSCLC patients with uncommon EGFR mutation. The primary endpoint of the study is objective response rate. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M (9). In this study, we expect an objective response rate of about 30% for the experimental arm (AZD9291 therapy) compared to that of about 10% in the historical control based on previous studies. A sample size of 33 efficacy-evaluable patients would provide a power of 90% for testing the null hypothesis of 10% ORR vs. alternative hypothesis of 30% using a single-arm exact binomial test with a 1=sided significance level of 5%. The experimental therapy will be rejected if 6 or fewer patients out of 33 respond. Allowing for a follow-up loss rate of 10%, the total sample size is 37 patients. Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). Subjects (with the exception of subjects with insulin dependent diabetes) must fast for ≥1 hours prior to taking a dose to ≥2 hour post dose. Water is permitted during this fasting period. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation. If the efficacy will be proven, the patient could receive the treatment continuously.