Updated overall survival (OS) and exploratory analysis from the randomized, phase II EVAN study of erlotinib (E) versus vinorelbine plus cisplatin (NP) as adjuvant therapy in Chinese patients with stage IIIA EGFR+ NSCLC.

Abstract

8520 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.