Background: EGFR mutant NSCLC is exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs). Retrospective data suggests adjuvant TKIs may improve outcomes. This trial is the first to prospectively test the efficacy of adjuvant erlotinib in EGFR-mutant NSCLC. Methods: Eligible pts had resected stage IA-IIIA NSCLC harboring a TKI-sensitizing EGFR mutation. Pts were treated with erlotinib 150 mg/day for 2 years after completion of standard adjuvant chemotherapy and/or radiotherapy. With a sample size of 100 pts the study was powered to demonstrate a primary endpoint of 2-year disease free survival (DFS) >85%, compared to a historical control of 76% in resected early-stage EGFR-mutant NSCLC. Results: 100 pts were enrolled at 7 sites between 1/08 and 5/12; 45% stage I; 27% stage II; 28% stage IIIA. 89 pts have reached 2 year follow-up (2 year follow-up on the entire cohort will be presented at the annual meeting). Toxicities were typical of erlotinib with no G4/5 events and 1 G2 pulmonary fibrosis. 40% of pts required dose reduction to 100 mg/day and 16% two dose reductions to 50 mg/day. 69% of pts completed at least 22 months of erlotinib. With median follow-up of 3 years, the 2-year DFS is 90% (97% stage 1, 73% stage 2, 92% stage 3). Median DFS and OS have not been reached. 24 pts have recurred, only 2 during erlotinib treatment and 22 after stopping erlotinib with a median time to recurrence of 12 months after stopping erlotinib. 63% (n=15) of pts with recurrence underwent repeat biopsy, and only 1 T790M was detected. 71% (n=17) of recurrent pts were re-treated with erlotinib with 10 pts remaining on erlotinib, treatment range 2-42 months. 8 pts have died. Conclusions: Pts with EGFR mutation-positive NSCLC treated with adjuvant erlotinib have an improved 2-year DFS compared to historical genotype-matched controls. Recurrences are rare on erlotinib and most occur in the 12m after discontinuation, suggesting longer duration of adjuvant treatment may be beneficial. Recurrent cases after adjuvant erlotinib remain generally sensitive to EGFR TKIs. Clinical trial information: NCT00567359.