Background: The EVAN study of E vs NP in stage III EGFR+ NSCLC has met its primary endpoint and been previously published: 2-year disease-free survival was 81.4% (95% CI, 69.6–93.1) in E group vs 44.6% (95% CI, 26.9-62.4) in NP group (HR, 1.823; 95% CI, 1.194–2.784; P=0.0054). We report 5-year OS and exploratory results from EVAN with a further 43 month follow up (cutoff date: Jan 6, 2021). Methods: Patients with stage IIIA EGFR+ NSCLC were randomized assigned (1:1) into either E arm (n=51, 150mg/day) or NP arm (n=51, vinorelbine 25mg/m² on day 1, 8 and cisplatin 75mg/m² on day 1 of a 21-day cycle). In order to explore the relationship between patient benefits and co-occurring variants, 47 patients received whole exome sequencing (WES) analysis (E, n=24; NP, n=23). Results: Median follow-up time was 54.8 months for E and 63.9 months for NP. E improved OS and 5-year survival rate compared with NP in ITT population. The median OS was 84.2m (95% CI, 78.1,-) with E vs 61.1m (95% CI, 39.6-82.1) with NP (HR, 0.318; 95% CI, 0.151-0.670). The 5-year survival rates were 84.8% (95%CI, 72.0-97.6) and 51.1% (95% CI, 34.7-67.5), respectively. In the WES analysis, we found that the most frequent genes with co-occurring variants at baseline were TP53, MUC16, FAM104B, KMT5A and DNAH9, and additional EGFR variants, each with similar prevalence regardless of EGFR-activating mutation subgroup. Moreover, in the erlotinib-treated patients, the SNP mutation of UBXN11 was associated with significantly worse DFS (P=0.0111). Conclusions: This is the first randomized study of EGFR-TKI to demonstrate a clinically meaningful improvement in OS vs chemotherapy in stage III EGFR+ NSCLC (5-year survival rate 84.8% in E vs 51.1% in NP). The co-occurring variants at baseline may be associated with reduced DFS. Further studies are required to confirm our results (EVAN, NCT01683175). Clinical trial information: NCT01683175