Background: Adjuvant chemotherapy after resection for early-stage NSCLC has been shown to improve long-term survival. However, the benefit is modest (4-15%) and many pts will still relapse due to the intrinsic chemoresistance of most lung cancers. Cancers with activating EGFR mutations represent a unique subset that is exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs) such as E, and TKIs have become the standard of care treatment for advanced NSCLC pts with these mutations. Adjuvant TKIs have not been studied in a genotype-specific population. We hypothesize that genotype-directed adjuvant TKI therapy may be effective in reducing recurrence rates among EGFR-mutant early-stage NSCLC patients. Methods: This is an open-label, single arm phase II study of adjuvant E in pts with resected, early-stage NSCLC with EGFR mutations (NCT00567359). Eligible pts have surgically resected stage IA-IIIA NSCLC and confirmed activating EGFR mutations, must be within 6 mos of surgery, and may have completed routine adjuvant treatment. Pts are treated with 150 mg/day of E for a total of 2 years, with surveillance scans every 3 months. The primary endpoint is disease-free survival (DFS) at 2 years. The planned sample size of 100 patients will provide 90% power to observe an improvement in DFS at 2 years from a historical control of 76% (estimated from a large single institution cohort of mutant NSCLC pts) to 86% for patients treated with adjuvant E. Secondary endpoints include safety and tolerability of adjuvant E, median DFS, and overall survival. When possible, biopsies will be obtained at the time of recurrence to document the mechanism of resistance to E. To date 69 of 100 patients have been enrolled at 6 institutions. Funding for this trial is provided by Genentech.